Reduced L-Arginine and L-Arginine-ADMA-Ratio, and Increased SDMA after Norseman Xtreme Triathlon.
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SUBMITTER: Nyborg C
PROVIDER: S-EPMC8472968 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:COVID-19 is a disease with a variable clinical course ranging from mild symptoms to critical illness, organ failure, and death. Prospective biomarkers may help to predict the severity of an individual's clinical course and mortality risk. We analyzed asymmetric (ADMA) and symmetric dimethylarginine (SDMA) in blood samples from 31 patients hospitalized for COVID-19. We calculated associations of ADMA and SDMA with mortality and organ failure, and we developed a predictive algorithm based upon these biomarkers to predict mortality risk. Nine patients (29%) experienced in-hospital death. SDMA and ADMA serum concentrations were significantly higher at admission in COVID-19 patients who died than in survivors. Cut-offs of 0.90 µmol/L for SDMA (AUC, 0.904, p = 0.0005) and 0.66 µmol/L for ADMA (AUC, 0.874, p = 0.0013) were found in ROC analyses to best discriminate both subgroups of patients. Hazard ratio for in-hospital mortality was 12.2 (95% CI: 2.2-31.2) for SDMA and 6.3 (1.1-14.7) for ADMA above cut-off. Sequential analysis of both biomarkers allowed discriminating a high-risk group (87.5% mortality) from an intermediate-risk group (25% mortality) and a low-risk group (0% mortality). Elevated circulating concentrations of SDMA and ADMA may help to better identify COVID-19 patients with a high risk of in-hospital mortality.
| S-EPMC8110746 | biostudies-literature
Project description:BACKGROUND:Nitric oxide (NO) regulates processes involved in sepsis progression, including vascular and immune function. NO is generated by nitric oxide synthases (NOS) from L-arginine. Cellular L-arginine uptake is inhibited by symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA) is a competitive inhibitor of NOS. Increased inhibitor blood concentrations lead to reduce NO bioavailability. The aim of this study was to determine whether plasma concentrations of SDMA and ADMA are markers for sepsis survival. METHOD:This prospective, single center study involved 120 ICU patients with sepsis. Plasma SDMA and ADMA were measured on admission (day 1), day 3 and day 7 by mass spectrometry together with other laboratory markers. The sequential organ failure assessment (SOFA) score was used to evaluate sepsis severity. Survival was documented until day 28. Groups were compared using the Mann-Whitney U test, chi-squared test or non-parametric analysis of variance (ANOVA). Mortality was assessed using Kaplan-Meier curves and compared using the log-rank test. Specific risk groups were identified using a decision tree algorithm. RESULTS:Median plasma SDMA and ADMA levels were significantly higher in non-survivors than in survivors of sepsis: SDMA 1.14 vs. 0.82 ?mol/L (P?=?0.002) and ADMA 0.93 vs. 0.73 ?mol/L (P?=?0.016). ANOVA showed that increased plasma SDMA and ADMA concentrations were significantly associated with SOFA scores. The 28-day mortality was compared by chi-square test: for SDMA the mortality was 12% in the lower, 25% in the intermediate and 43% in the 75th percentile (P?=?0.018); for ADMA the mortality was 18-20% in the lower and intermediate but 48% in the 75th percentile (P?=?0.006). The highest mortality (61%) was found in patients with plasma SDMA >?1.34 together with ADMA levels >?0.97 ?mol/L. CONCLUSIONS:Increased plasma concentrations of SDMA and ADMA are associated with sepsis severity. Therefore, our findings suggest reduced NO bioavailability in non-survivors of sepsis. One may use individual SDMA and ADMA levels to identify patients at risk. In view of the pathophysiological role of NO we conclude that the vascular system and immune response are most severely affected when SDMA and ADMA levels are high.
| S-EPMC6145330 | biostudies-literature
Project description:Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are endogenous inhibitors of nitric oxide (NO) synthesis, and play a critical role in the process of endothelial dysfunction, and are considered markers of oxidative stress. The aim of the present study was to explore relationships between ADMA and/or SDMA and the occurrence of OSA in obese patients as well as the effect of the endothelial nitric oxide synthase (eNOS) gene polymorphism, which may modify the influence of ADMA or SDMA on NO production. A total of 518 unrelated obese subjects were included in this study. Body weight, height and blood pressure were measured and data on self-reported smoking status were collected. Obstructive sleep apnea (OSA) was assessed by the apnea hypopnea index (AHI). Blood samples were collected to measure serum concentrations of glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, creatinine, HbA1c (%), folic acid, vitamin B12, C-reactive protein (CRP), aspartate aminotransferase (ASP), alanine aminotransferase (ALT) and IL-6 by routine methods. The NOS3 gene G894T and 4a/4b polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. ADMA, SDMA and arginine concentrations were assessed simultaneously using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method. Adjusted multivariate logistic regression analysis showed a significant association between the occurrence of OSA and high serum ADMA levels, BMI above 40, age > 43 years, hypertension and male sex. Heterozygotes for the G894T eNOS polymorphism have the lowest serum concentrations of ADMA and SDMA, while no effect of the 4a/4b variants was observed. The results indicate that OSA in obese individuals can coexist with high ADMA levels, which appear as a potential OSA predictor.
| S-EPMC6616493 | biostudies-literature
Project description:Arginine deficiency may contribute to microvascular dysfunction, but previous studies suggest that arginine supplementation may be harmful in sepsis. Systemic arginine availability can be estimated by measuring the ratio of arginine to its endogenous inhibitors, asymmetric and symmetric dimethylarginine. We hypothesized that the arginine-to-dimethylarginine ratio is reduced in patients with severe sepsis and associated with severity of illness and outcomes.Case-control and prospective cohort study.Medical and surgical intensive care units of an academic medical center.One hundred nine severe sepsis and 50 control subjects.Plasma and urine were obtained in control subjects and within 48 hrs of diagnosis in severe sepsis patients. The arginine-to-dimethylarginine ratio was higher in control subjects vs. sepsis patients (median, 95; interquartile range, 85-114; vs. median, 34; interquartile range, 24-48; p < .001) and in hospital survivors vs. nonsurvivors (median, 39; interquartile range, 26-52; vs. median, 27; interquartile range, 19-32; p = .004). The arginine-to-dimethylarginine ratio was correlated with Acute Physiology and Chronic Health Evaluation II score (Spearman's correlation coefficient [?] = - 0.40; p < .001) and organ-failure free days (? = 0.30; p = .001). A declining arginine-to-dimethylarginine ratio was independently associated with hospital mortality (odds ratio, 1.63 per quartile; 95% confidence interval, 1.00-2.65; p = .048) and risk of death over the course of 6 months (hazard ratio, 1.41 per quartile; 95% confidence interval, 1.01-1.98; p = .043). The arginine-to-dimethylarginine ratio was correlated with the urinary nitrate-to-creatinine ratio (? = 0.46; p < .001).The arginine-to-dimethylarginine ratio is associated with severe sepsis, severity of illness, and clinical outcomes. The arginine-to-dimethylarginine ratio may be a useful biomarker, and interventions designed to augment systemic arginine availability in severe sepsis may still be worthy of investigation.
| S-EPMC3292345 | biostudies-literature
Project description:Kidney disease is common in companion animals, and traditionally diagnosed with serum creatinine concentration (sCr), blood urea nitrogen, and abnormal urinalysis findings. Symmetric dimethylarginine (SDMA) is a novel kidney biomarker that reflects glomerular filtration rate, increasing earlier than sCr with acute kidney injury and chronic kidney disease. This prospective study compared accuracy and precision of two commercial SDMA assays, the IDEXX SDMA Test and the DLD SDMA ELISA, relative to the established reference method, liquid chromatography/mass spectrometry (LC-MS). Thirty canine and 30 feline pooled serum samples were used to evaluate accuracy compared to LC-MS. Pooled canine samples with a low SDMA concentration and pooled feline samples with a high SDMA concentration were used to evaluate precision. Using a best fit linear model, the IDEXX SDMA Test resulted in a slope of 1.06 and an intercept of 0.34, with R2 = 0.99, and the DLD SDMA ELISA resulted in a slope of 0.37 and an intercept of 11.33, with R2 = 0.27, when compared to LC-MS. Estimated bias over a clinically relevant range for SDMA (10-45 μg/dL) was 1-2 μg/dL for the IDEXX SDMA Test, while DLD SDMA ELISA showed considerable bias, 5-8 μg/dL. Day-to-day precision analysis of the low SDMA concentration samples showed 7.7% total coefficient of variation (CV) for the IDEXX SDMA Test and 31.1% for the DLD SDMA ELISA. For the high SDMA concentration samples, total CV was 2.3% for the IDEXX SDMA Test and 28.2% for the DLD SDMA ELISA. In this study the IDEXX SDMA Test was more accurate and more precise in macroscopically normal serum than the DLD SDMA ELISA when compared to the reference method of LC-MS. The IDEXX SDMA Test is more suitable for clinical use in the diagnosis and monitoring of kidney disease in dogs and cats.
| S-EPMC6188631 | biostudies-literature
Project description:ObjectiveEven though ˪-arginine (ARG) derivatives can predict cardiovascular mortality, their role as atherosclerotic biomarkers is unclear. We tested the hypothesis if asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and the sum of both (DMA) are positively, while ARG and ARG/ADMA ratio are inversely associated with carotid intima-media thickness (cIMT) and atherosclerotic plaque in the carotid artery.Approach and resultsCross-sectional data of 1999 subjects (age: 45-81 years; 48.2% ♀) from the population-based Study of Health in Pomerania (SHIP-0) was used. Analysis of variance and logistic regression models were calculated and all adjusted models were corrected for sex, age, smoking status, waist-to-hip ratio and estimated glomerular filtration rate. Increased cIMT (>75th age-sex specific percentile) was found in 517 subjects (25.7%), while atherosclerotic plaque was detected in 1413 subjects (70.4%). SDMA tertiles were significantly positively associated with larger cIMT among subjects with high SDMA levels [>66th: 0.82 (95%-CI 0.80; 0.85) mm]. High SDMA levels were related to a higher odds ratio (OR) of increased cIMT [OR 1.39 (95%-CI 1.08; 1.79)]. Furthermore, ARG was positively associated with atherosclerotic plaques [OR 1.41 (95%-CI 1.07; 1.85)]. No relation was found for ADMA and atherosclerosis.ConclusionsIn conclusion, the hypothesis of a positive association between SDMA with an increased cIMT was confirmed. Unexpectedly, ARG was positively related to atherosclerotic plaque. In view of these inconsistent findings, the impact of ARG derivatives as atherosclerotic biomarkers deserves further research.
| S-EPMC4476678 | biostudies-literature
Project description:BackgroundCarnitine-acylcarnitine translocase (CACT) deficiency is a rare autosomal recessive metabolic disorder of mitochondrial long-chain fatty acid oxidation. Newborn screening via tandem mass spectrometry (MS/MS) technology enables early diagnosis. However, previous analyses of MS/MS data of patients showed that some results were misdiagnosed because they did not show typical acylcarnitine profiles of CACT deficiency. This study aimed to identify additional indices to assist the diagnosis of CACT deficiency.MethodsTo evaluate the acylcarnitine profile and the acylcarnitine ratios of individuals with CACT deficiency, the MS/MS data of 15 patients diagnosed via genetic testing were retrospectively analysed. The sensitivity and false-positive rates of primary acylcarnitine markers and ratio indices were validated using the data from 28,261 newborns and 53 false-positive cases. Additionally, the MS/MS data of 20 newborns carrying the c.199-10T>G mutation in SLC25A20 and 40 normal controls were compared to verify whether the carriers had abnormal acylcarnitine concentrations.ResultsThe acylcarnitine profiles from 15 patients were classified into three categories using C12, C14, C16, C18, C16:1, C18:1, and C18:2 as the primary diagnostic markers. The first category represented a typical profile (P1-P6). The second category for patients P7 and P8 showed a significant decrease in the C0 level and a normal concentration of long-chain acylcarnitines. The third category for patients P9-P15 showed the presence of interfering acylcarnitines. The second and third categories may have been misdiagnosed. An acylcarnitine ratio analysis showed that C14/C3, C16/C2, C16/C3, C18/C3, C16:1/C3, and C16:1-OH/C3 were significantly increased in all 15 patients. The verification of 28,261 newborn screening results showed that the false-positive rate of ratios, except for (C16 + C18)/C0, was lower than that of acylcarnitine indices (0.02-0.08% vs. 0.16-0.88%). None of the single long-chain acylcarnitines could separate patients from the false-positive cases; however, all ratios produced good discrimination between the two groups.ConclusionsBased on the primary acylcarnitine markers alone, CACT deficiency can be misdiagnosed in newborn screening. The ratios of the primary markers (C16 + C18:1)/C2, C16/C2, C16:1/C3, and C16:1-OH/C3 can facilitate the diagnosis of CACT deficiency, thereby increasing sensitivity and reducing false-positivity.
| S-EPMC10248924 | biostudies-literature
Project description:We hypothesized that an integrated assessment of arginine with its catabolic products might better predict cardiovascular risks than arginine levels alone.Arginine is the sole nitrogen source for nitric oxide (NO) synthesis. The major catabolic products of arginine are ornithine and citrulline.Plasma levels of free arginine, ornithine, citrulline, and the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) were measured with liquid chromatography coupled with tandem mass spectrometry. We examined the relationship of global arginine bioavailability ratio (GABR) (defined as arginine/[ornithine + citrulline]) versus arginine and its catabolic metabolites to prevalence of significantly obstructive coronary artery disease (CAD) and incidence of major adverse cardiovascular events (MACE) (death, myocardial infarction, stroke) over a 3-year follow-up in 1,010 subjects undergoing elective cardiac catheterization.Patients with significantly obstructive CAD had significantly lower GABR (median [interquartile range]: 1.06 [0.75 to 1.31] vs. 1.27 [0.96 to 1.73], p < 0.001) and arginine levels [mean: 68 +/- 20 micromol/l vs. 74 +/- 24 micromol/l, p < 0.001) than those without significantly obstructive CAD. After adjusting for Framingham risk score, C-reactive protein, and renal function, lower GABR (but not arginine levels) and higher citrulline levels remained significantly associated with both the prevalence of significantly obstructive CAD (adjusted odds ratio: 3.93, p < 0.001, and 5.98, p < 0.001, respectively) and 3-year risk for the incidence of MACE (adjusted hazard ratio: 1.98, p = 0.025, and 2.40, p = 0.01, respectively) and remained significant after adjusting for ADMA.GABR might serve as a more comprehensive concept of reduced NO synthetic capacity compared with systemic arginine levels. Diminished GABR and high citrulline levels are associated with both development of significantly obstructive atherosclerotic CAD and heightened long-term risk for MACE.
| S-EPMC2755213 | biostudies-literature
Project description:The mechanisms promoting disturbed white adipocyte function in obesity remain largely unclear. Herein, we integrate white adipose tissue (WAT) metabolomic and transcriptomic data from clinical cohorts and find that the WAT phosphocreatine/creatine ratio is increased and creatine kinase-B expression and activity is decreased in the obese state. . In human in vitro and murine in vivo models, we demonstrate that decreased phosphocreatine metabolism in white adipocytes alters AMPK activity via effects on ATP/ADP levels, independently of WAT beigeing. This disturbance promotes a pro-inflammatory profile characterized, in part, by increased CCL2 production. These data suggest that the phosphocreatine/creatine system links cellular energy shuttling with pro-inflammatory responses in human and murine white adipocytes. Our findings provide unexpected perspectives on the mechanisms driving WAT inflammation in obesity and may present avenues to target adipocyte dysfunction.
2022-01-27 | GSE192361 | GEO
Project description:Prolonged exercise is known to cause changes in common biomarkers. Occasionally, competition athletes need medical assistance and hospitalisation during prolonged exercise events. To aid clinicians treating patients and medical teams in such events we have studied common biomarkers after at The Norseman Xtreme Triathlon (Norseman), an Ironman distance triathlon with an accumulated climb of 5200 m, and an Olympic triathlon for comparison. Blood samples were collected before, immediately after, and the day following the Norseman Xtreme Triatlon (n = 98) and Oslo Olympic Triathlon (n = 15). Increased levels of clinical significance were seen at the finish line of the Norseman in white blood cells count (WBC) (14.2 [13.5-14.9] 109/L, p < 0.001), creatinine kinase (CK) (2450 [1620-3950] U/L, p < 0.001) and NT-proBNP (576 [331-856] ng/L, p < 0.001). The following day there were clinically significant changes in CRP (39 [27-56] mg/L, p < 0.001) and Aspartate Aminotransferase (AST) (142 [99-191] U/L, p < 0.001). In comparison, after the Olympic triathlon distance, there were statistically significant, but less clinically important, changes in WBC (7.8 [6.7-9.6] 109/L, p < 0.001), CK (303 [182-393] U/L, p < 0.001) and NT-proBNP (77 [49-88] ng/L, p < 0.01) immediately after the race, and in CRP (2 [1-3] mg/L, p < 0.001) and AST (31 [26-41] U/L, p < 0.01) the following day. Subclinical changes were also observed in Hemoglobin, Thrombocytes, K+, Ca2+, Mg2+, Creatinine, Alanine Aminotransferase and Thyroxine after the Norseman. In conclusion, there were significant changes in biomarkers used in a clinical setting after the Norseman. Of largest clinical importance were clinically significant increased WBC, CRP, AST, CK and NT-proBNP after the Norseman. This is important to be aware of when athletes engaging in prolonged exercise events receive medical assistance or are hospitalised.
| S-EPMC7510962 | biostudies-literature