Serum Asymmetric Dimethylarginine Levels Research Articles

Asymmetric dimethylarginine correlates with worsening peripheral microangiopathy in systemic sclerosis.

Systemic sclerosis (SSc) is a connective tissue disease characterized primarily by micro-angiopathy and endothelial dysfunction which stimulate a fibrotic process. Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide (NO) inhibitor and represents a novel biomarker for vascular dysfunction. Nailfold video capillaroscopy (NVC) represents a non-invasive and reliable technique for the evaluation of microvasculopathy in SSc. The aim of this study was to examine the possible association between ADMA and microvascular involvement in patients with SSc. This was a cross-sectional study including consecutive SSc patients attending the Scleroderma Outpatient Clinic. ADMA was measured in serum samples using a commercial enzyme immunoassay. Participants underwent NVC with qualitative and semi-quantitative assessment and all NVC parameters were measured in the distal row of each finger. The findings were classified in one of the three qualitative NVC patterns: early, active, and late. Eighty-one (92,6% women) SSc individuals with mean age 55.44±13.4years were included in this analysis. Within-groups comparisons revealed a trend between higher ADMA levels and progressive micro-vasculopathy (1,29 [2,1] vs 1,57 [1,95] vs 2,41 [3,87]; for early, active and late patterns respectively, p=0.039). Furthermore, ADMA concentration was significantly associated with the number of capillaries/mm (r=-0.235; p=0.035). Serum ADMA levels were significantly associated with advancing stages of microcirculatory abnormalities suggesting that ADMA may have a role in promoting microvascular endothelial dysfunction in SSc individuals.

Elevated VCAM-1, MCP-1 and ADMA serum levels related to pulmonary fibrosis of interstitial lung disease associated with rheumatoid arthritis.

Introduction: Early diagnosis of interstitial lung disease (ILD) associated with rheumatoid arthritis (RA) constitutes a challenge for the clinicians. Pulmonary vasculopathy is relevant in the development of interstitial lung disease. Accordingly, we aimed to explore the role of vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1) and asymmetric dimethylarginine (ADMA), key molecules in the vasculopathy, as potential biomarkers of pulmonary fibrosis in RA-ILD+. Methods: We included 21 RA-ILD+ patients and two comparative groups: 25 RA-ILD- patients and 21 idiopathic pulmonary fibrosis (IPF) patients. Serum levels of the molecules were determined by ELISA, and mRNA expression was quantified by qPCR. Results: VCAM-1, MCP-1 and ADMA serum levels were increased in RA-ILD+ patients in relation to RA-ILD- and IPF patients. Additionally, RA-ILD+ patients exhibited increased CCL2 (gene encoding MCP-1) and decreased PRMT1 (gene related to ADMA synthesis) mRNA expression in relation to RA-ILD- patients. A lower expression of VCAM1, CCL2, and PRMT1 was observed in RA-ILD+ patients when compared with those with IPF. Furthermore, MCP-1 serum levels and PRMT1 mRNA expression were positively correlated with RA duration, and ADMA serum levels were positively associated with C-reactive protein in RA-ILD+ patients. Conclusion: Our study suggests that VCAM-1, MCP-1 and ADMA could be considered as useful biomarkers to identify ILD in RA patients, as well as to discriminate RA-ILD+ from IPF, contributing to the early diagnosis of RA-ILD+.

The effect of haptoglobin genotype on the association of asymmetric dimethylarginine and DDAH 1 polymorphism with diabetic macroangiopathy

BackgroundDimethylarginine dimethylaminohydrolase (DDAH) 1 maintains the bioavailability of nitric oxide by degrading asymmetric dimethylarginine (ADMA). Here, we aimed to investigate the effect of haptoglobin (Hp) genotype on the association of ADMA and DDAH 1 polymorphism with diabetic macroangiopathy.MethodsIn stage 1, 90 Chinese participants with type 2 diabetes were enrolled to measure a panel of targeted metabolites, including ADMA, using tandem mass spectrometry (BIOCRATES AbsoluteIDQ™ p180 kit). In stage 2, an independent cohort of 2965 Chinese patients with type 2 diabetes was recruited to analyze the effect of Hp genotype on the association between DDAH 1 rs233109 and diabetic macroangiopathy. Hp genotypes were detected using a validated assay based on the TaqMan method. DDAH 1 rs233109 was genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy using the MassARRAY platform.ResultsIn stage 1, serum ADMA levels correlated with common Hp genotypes (β ± SE = − 0.049 ± 0.023, P = 0.035), but not with diabetic macroangiopathy (P = 0.316). In stage 2, the distribution of DDAH 1 rs233109 genotype frequencies was 15% (CC), 47% (TC), and 38% (TT), which was in Hardy-Weinberg equilibrium (P = 0.948). A significant Hp genotype by rs 233109 genotype interaction effect on diabetic macroangiopathy was found (P = 0.017). After adjusting for confounders, patients homozygous for rs233109 CC were more likely to develop diabetic macroangiopathy than those carrying TT homozygotes in the Hp 2-2 subgroup [odds ratio = 1.750 (95% confidence interval, 1.101–2.783), P = 0.018].ConclusionHp genotype affects the association between DDAH 1 rs233109 and diabetic macroangiopathy in Chinese patients with type 2 diabetes.

The ADMA–DDAH1 axis in ovarian apoptosis of polycystic ovary syndrome

Dimethylarginine dimethylaminohydrolase 1 (DDAH1) mainly degrades asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor. Emerging evidence suggested that plasma ADMA is accumulated in patients with polycystic ovary syndrome (PCOS). However, ADMA–DDAH1 involvement in PCOS pathogenesis is unclear. Here, we used dehydroepiandrosterone (DHEA)-induced PCOS rats and the ovarian granulosa cell line KGN to investigate the effect of the ADMA–DDAH1 pathway on ovarian apoptosis. Moreover, we also quantified the ADMA levels and redox status in human serum specimens, Sprague Dawley rats and KGN cells to investigate the effect of ADMA–DDAH1 on redox status and ovarian apoptosis in PCOS. We enrolled 19 women with PCOS and 17 healthy women (controls) in this study. The women with PCOS had increased serum ADMA levels and decreased glutathione peroxidase (GSH-PX) compared with the controls. In Sprague Dawley rats, 21-day DHEA treatment established PCOS and the rat contained higher ADMA levels in serum and lower DDAH1 expression in ovaries. Moreover, the PCOS rat serum and ovaries exhibited increased levels of the oxidative stress marker malondialdehyde (MDA). ADMA treatment of the KGN cells induced reactive oxygen species accumulation and led to apoptosis. Contrastingly, overexpressing DDAH1 in the KGN cells significantly decreased ADMA levels, enhanced cell viability, and inhibited oxidative stress, while the effect was inverse in DDAH1 knockdown cells. Overall, our results demonstrated that PCOS involves elevated ADMA levels and redox imbalance. The ADMA–DDAH1 pathway exerted a marked effect on oxidative stress and ovarian apoptosis in PCOS. Our findings suggested that strategies for increasing DDAH1 activity in ovarian cells may provide a novel approach for ameliorating PCOS.

Raised total methylated arginine load in patients with gout.

Aim: The aim of this study was to measure serum levels of methylarginine derivatives and related metabolites in patients with gout. Materials & methods: This study enrolled 100 patients with gout and 80 patients in the control group. Serum asymmetric dimethylarginine, symmetric dimethylarginine, L-N-monomethylarginine, arginine, homoarginine, citrulline and ornithine levels were measured with tandem mass spectrometry. Results: Serum ornithine, citrulline and total methylated arginine load levels were statistically significantly higher in patients with gout compared with the control group, while serum arginine and homoarginine levels and global arginine bioavailability ratio were statistically significantly lower. Conclusion: There may be an association between gout, methylarginine levels and hyperuricemia and increased risk of cardiovascular disease.

Effects of Ramipril on Biomarkers of Endothelial Dysfunction and Inflammation in Hypertensive Children on Maintenance Hemodialysis: the SEARCH Randomized Placebo-Controlled Trial.

Hypertension, endothelial dysfunction, and inflammation are associated with increased cardiovascular mortality in end-stage kidney disease. We evaluated the effects of ACE (angiotensin-converting enzyme) inhibition on biomarkers of endothelial dysfunction and inflammation in hypertensive children with end-stage kidney disease on maintenance hemodialysis. In a randomized, double-blind, placebo-controlled trial, 135 (72 males/63 females) children and adolescents (age 7-15 years) were randomly assigned to treatment with either 2.5 mg once daily ramipril (n=68) or placebo (n=67) for 16 weeks. Primary outcome were the serum concentrations of asymmetrical dimethylarginine, a marker of endothelial dysfunction and hs-CRP (high-sensitivity C-reactive protein), a marker of inflammation. Changes in IL-6 (interleukin-6), TNF-α (tumor necrosis factor-alpha), systolic (S), and diastolic (D) blood pressure were secondary outcomes. Change in potassium levels and incidence of hyperkalemia were among the safety parameters. Ramipril, but not placebo, significantly reduced serum levels of asymmetrical dimethylarginine (-79.6%; P<0.001), hs-CRP (-46.5%; P<0.001), IL-6 (-27.1%; P<0.001), and TNF-α (-51.7%; P<0.001). Systolic blood pressure and diastolic blood pressure were significantly lowered in both groups with a greater reduction in children receiving ramipril (median between-group differences -12.0 [95% CI -18.0 to -9.5] and -9.0 [95% CI -12.0 to -4.5]; P<0.001, respectively). Changes in asymmetrical dimethylarginine, hs-CRP, IL-6, or TNF-α in the ramipril group did not significantly correlate with blood pressure reductions. No severe cases of hyperkalemia or other serious treatment-associated adverse events were observed. Ramipril improves biomarkers of endothelial dysfunction and inflammation in hypertensive children on maintenance hemodialysis in addition to its efficacious and safe potential to lower blood pressure. URL: https://www. gov; Unique identifier: NCT04582097.

Serum miR-204 and miR-451 Expression and Diagnostic Value in Patients with Pulmonary Artery Hypertension Triggered by Congenital Heart Disease.

Objective To determine the level of expression and clinical importance of serum miR-204 and miR-451 in patients with pulmonary arterial hypertension caused by congenital heart disease (CHD-PAH). Methods From July 2019 to January 2021, 114 infants with congenital heart disease (CHD) were hospitalized at Qingdao's Fuwai Cardiovascular Hospital. They were grouped into categories: CHD (53 cases) and CHD-PAH (61 cases) based on whether they had pulmonary hypertension (PAH). In addition, 60 healthy children were selected as the control group. All children underwent routine biochemical examination, echocardiography, and pulmonary arterial pressure examination. By using an enzyme-linked immunosorbent assay (ELISA), the levels of brain natriuretic peptide (BNP) and asymmetric dimethylarginine (ADMA) in the blood were measured. Additionally, reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the expression levels of miR-204 and miR-451 in peripheral blood. The correlation between miR-204, miR-451, BNP, ADMA, and mPAP was investigated using Pearson correlation analysis. Results Consequently, the TC, BNP, and ADMA serum levels were considerably higher in the CHD and CHD-PAH groups than in the control group (P < 0.05), whereas BNP and ADMA serum levels were significantly higher in the CHD-PAH group than in the CHD group (P < 0.05). According to RT-PCR data, the expression levels of miR-204 and miR-451 in the peripheral blood of children in the CHD and CHD-PAH groups were significantly lower (P < 0.05) when compared to the control group. The expression levels of miR-204 and miR-451 in the peripheral blood of children in the CHD-PAH group were substantially lower (P < 0.05) than in the CHD group. Significantly, the findings of the ROC curve revealed that the area under the curve (AUC) of CHD-PAH diagnosed by miR-204 and miR-451 alone was 0.737 and 0.725, respectively, and the AUC of joint diagnosis was 0.840, which was greater than that of single diagnosis (P < 0.05). Patients with CHD-PAH had lower levels of miR-204 and miR-451 in their blood, and this was found to be associated with BNP, ADMA, and mPAP, analyzed by Pearson correlation. Conclusions Children with CHD-PAH can be diagnosed based on aberrant expressions of miR-204 and miR-451 in their peripheral blood serum. Moreover, CHD-PAH can be diagnosed if the combination of miR-204 and miR-451 is detected as a biomarker, which has a higher diagnostic value.

Biomarkers of endothelial dysfunction and atherosclerosis in hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with an increased prevalence of subclinical atherosclerosis and cardiovascular risk. Angiopoietin-2 (Ang-2), asymmetric dimethylarginine (ADMA), and osteoprotegerin (OPG) are molecules related to endothelial dysfunction (ED) and atherosclerosis, but also to disease severity in patients with chronic inflammatory disorders. In this case-control study, we aimed to investigate serum Ang-2, ADMA, and OPG levels in patients with HS, and to assess the potential relationship between these levels and disease severity. Seventy-five patients with HS and 60 controls were assessed. Serum Ang-2, ADMA, and OPG concentrations were determined in all participants. HS patients had significantly higher Ang-2 and ADMA levels than controls after adjusting for confounders. Besides, Ang-2 concentrations positively correlated with disease severity in the adjusted multivariable analysis. Nevertheless, serum OPG levels did not significantly differ between HS patients and controls. Our results indicate that serum Ang-2 and ADMA levels are significantly increased in patients with HS. Furthermore, Ang-2 might be a suitable marker of HS severity.

Quantification of serum homoarginine, methylated arginine and inhibin-A levels in a high-risk pregnancy

The plasma levels of homoarginine (h-Arg) and methylated arginine have proven to be an independent cardiovascular risk factor. We aimed to determine the h-Arg and methyl arginine levels in serums of high-risk pregnancy causing potential complications. These participants were divided into four groups as the control group with quadruple test, the high-risk group quadruple test the control group with binary test, the high-risk group with quadruple test that have a positive result from second-trimester screening with a cut-off value of 1 in 300. The serum methyl arginine and homoarginine levels were analysed with liquid chromatography-tandem mass spectrometry. Serum h-Arg levels were found to be higher in high-risk groups compared to control groups and it was also detected higher in the groups with quadruple test than the groups with binary test (p < .05). H-Arg levels in the groups showed strong negative correlation with age and serum inhibin-A levels (r = −0.288, p < .001). Also, there was a strong negative correlation between serum asymmetric dimethylarginine (ADMA) and serum inhibin-A levels (r = −0.352, p < .001). H-Arg may be a new risk marker to detect high-risk pregnancies in early pregnancy. In addition to, methylated arginine such as ADMA has a key regulator in a physiological concentration of h-Arg. IMPACT STATEMENT What is already known on this subject? H-Arg levels decrease may be associated with preeclampsia, GDM, macrosomia, low birth weight, and preterm delivery in pregnancy. What do the results of this study add? Serum h-Arg levels were found to be higher in high-risk groups. Additionally, h-Arg levels and ADAM, one of the methylated arginines in the groups showed a strong negative correlation with serum inhibin-A levels What are the implications of these findings for clinical practice and/or further research? H-Arg may be a new risk marker to detect high-risk pregnancies

Asymmetric dimethylarginine serum levels are associated with patient characteristics after renal transplant

Objectives: To investigate the changes in asymmetric plasma dimethylarginine (ADMA) levels after six months of renal transplant and their potential associations with patient characteristics. Subjects and methods: From March 2018 to April 2020, a prospective enrolled 75 recipients 6 months after renal transplant at Military Hospital 103. Results: The average ADMA concentration at 6th month of the transplant was 0.57 µmol/L, a statistically significant decrease from the time before transplant (0.62 µmol/L) with p &lt; 0.05, but still higher than the healthy controls (0.17 µmol/L), p &lt; 0.001. At 6th month following the transplant, 32.0% of patients had an increase and 68.0% had a decrease in ADMA concentration. After transplant, increased ADMA concentration was found to be positively correlated with the atherogenesis index (r = 0,468) and negatively correlated with the glomerular filtration rate (r = -0.261, p &lt; 0.05). Conclusion: Six months after renal transplant, plasma ADMA decreased significantly but remained higher than in healthy people. Following the transplant, both the atherogenesis index and the glomerular filtration rate were significantly associated with an increase in ADMA levels. * Keywords: Asymmetric Dimethylarginine;

Altered Arginine/Nitric Oxide Pathway in Children Diagnosed Attention Deficit Hyperactivity Disorder, and the Effect of 10 Weeks Methylphenidate Treatment.

ObjectiveIn this study, we investigated the levels of arginine, nitric oxide (NO), asymmetric dimethylarginine (ADMA), and adrenomedullin that are presumed to play a role in attention deficit hyperactivity disorder (ADHD) etiology, and to compare the findings with healthy controls.MethodsThirty ADHD patients and thirty healthy control subjects aged 6−12 years were included in the study. Sociodemographic data form, Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version; Conners’ Parent/Teacher Rating Scale-Revised Long Form; Children’s Depression Inventory; and The State-Trait Anxiety Inventory for Children were applied to all cases. All participants included in the study were evaluated in terms of their serum arginine, NO, ADMA, and adrenomedullin levels. Subsequently, methylphenidate treatment was started in ADHD patients and blood parameters were tested again in the tenth week of treatment.ResultsAt the start of the study, arginine and ADMA levels were significantly higher and NO and adrenomedullin levels were significantly lower in the ADHD group compared to the control group. Post-treatment arginine and ADMA levels were found to be significantly lower than in the pre-treatment period. There were no significant differences in NO and adrenomedullin levels before and after treatment. There was no correlation between scale scores and blood parameters.ConclusionThese variations in the blood parameters of the ADHD group seem to be worth further investigation. Studies to be conducted with larger sample groups after longer-term treatment may provide new information about the alterations in neurobiological processes related to ADHD etiology and treatment.

Relationship Between Serum Asymmetric Dimethylarginine Level and Obstructive Sleep Apnea Syndrome Severity

Aim: The repetitive hypoxemia can induce oxidative stress mechanisms. Oxidative stress increases serum asymmetric dimethylarginine (ADMA) levels in patients with obstructive sleep apnea syndrome (OSAS). To investigate the relationship between serum levels of ADMA and OSAS severity. Methods: 330 patient’s records, who underwent overnight poly-somnography (PSG) were retrospectively examined. The patients who had an abnormal serum glucose, lipid, thyroid, renal and liver function tests levels, had excluded. 72 patients had participating criteria. Patients were categorized into five groups according to apnea/hipopnea index (AHI). Measurement of ADMA levels were performed by ELISA kit. Results: The mean age was 44,19 ± 14,24 years. 31,9 % of the patients were female. Patients in normal group, severe, medium, mild and positional–REM dependent OSAS group were 26,4%, 25%, 6,9 %, 16,7% and 25%; respectively. A significant positive correlation was found between AHI and ADMA (r= 0,483; p&lt;0,001). Appropriate cut-off criterion was set at 1,39 for ADMA. Sensitivity for this value was 73,58 % (95 % Confidence Interval (CI): 61,71- % 85,45 %) and specificity was 94,74 % (95 % CI: 84,70- % to 100%). Accuracy or correct classification rate was found to be 79,17 %. The positive predictive value was 97,5 % and negative predictive value was 56,25 %. The positive likelihood ratio (LR +) was 13,98 (LR + &gt; 10) and the negative likelihood ratio was (LR-) 0,28 (R- &lt;1). Conclusions: ADMA was found to be a strong and good diagnostic tool among patients with normal levels for glucose, lipid, TSH, creatinine and liver function tests.

Serum asymmetric dimethylarginine (ADMA) level and cognitive dysfunction in diabetic patients

Serum asymmetric dimethylarginine (ADMA) level and cognitive dysfunction in diabetic patients

Effects of Physical Prehabilitation on the Dynamics of the Markers of Endothelial Function in Patients Undergoing Elective Coronary Bypass Surgery.

Our aim in this study was to evaluate the effect of physical training performed before CABG on the perioperative dynamics of the serum levels of asymmetric dimethylarginine (ADMA) and endothelin-1 (ET-1) of patients with stable coronary heart disease (CHD). Patients in the preoperative period were randomized into two groups: the training group (n = 43) underwent high-intensity treadmill training; the patients in the control group (n = 35) received no training before the procedure. The serum concentrations of ADMA and ET-1 were determined in the perioperative period, and the course of the early postoperative period was analyzed. In the training group, we found a significantly lower incidence of postoperative complications during hospital stays (p = 0.013). At the end of the training program, the ADMA levels were 1.8 times higher in the controls than in the training group (p = 0.001). We found that type 2 diabetes increased the probability of complications by 12 times (OR: 12.3; 95% CI: 1.24–121.5; p = 0.03), as well as elevating the concentration of ET-1 on the eve of surgery (OR: 10.7; 95% CI: 1.4–81.3; p = 0.02). Physical prehabilitation reduced the likelihood of complications nine times (OR: 0.11; 95% CI: 0.02–0.83; p = 0.03). The AUC was 0.851 ± 0.07 (95% CI: 0.71–0.98). The obtained results indicate the benefit of physical training during the prehabilitation stage since it can help to preserve endothelial function.

Effects of green cardamom supplementation on serum levels of Hs-CRP, dimethylarginine, nitric oxide and blood pressure in patients with type 2 diabetes: A randomized, double-blind, placebo controlled, clinical trial

PurposeCardamom contains phytochemicals with a potential role in lowering blood pressure (BP) and improving the inflammatory status in type 2 diabetes mellitus (T2DM). However, only a few studies have been carried out to evaluate the effect of cardamom in these patients. Therefore, the aim of this study was to assess the effects of green cardamom supplementation on serum high-sensitivity C–reactive protein (hs-CRP), asymmetric dimethylarginine (ADMA), nitric oxide (NO), systolic blood pressure (SBP) and diastolic blood pressure (DBP) in patients with T2DM. Materials and MethodsIn this double blind, randomized, controlled clinical trial, 83 patients with T2DM were divided randomly into two groups, including the green cardamom group (3 g/d, n = 41) and placebo group (3 g/d, n = 42). All patients received the supplements for 10 weeks. Serum levels of hs-CRP, ADMA, NO, SBP and DBP were measured at baseline and week 10. ResultsThe intention-to-treat (ITT) analysis showed a decrease in mean serum hs-CRP levels [from 5.22 (3.56) to 4.81 ng/ml (3.72); p < 0.05] along with a significant increase in mean serum NO levels [from 65.6 (22.6) to 84 Mµ (26.3)], (p < 0.001). There was a significant decrease in mean SBP in the cardamom group [from 125.2 (12.4) to 119.4 mm/hg (11.8)] compared to the placebo group [128.1 (15.6) to 126.7 mmHg (13.5)] (p < 0.001). Furthermore, ITT analysis showed a decrease in mean SBP [from 125.6 (12.2) to 120 mmHg (11.59)] (p < 0.001). Changes in serum ADMA and DBP levels were not statistically significant between the two groups. In addition, in Per-Protocol (PP) analysis, a significant decrease was found in mean serum hs-CRP levels in the cardamom group [from 5.25 (3.66) to 4.87 ng/ml (3.8)] compared to the placebo group [4.4 (3) to 5.7 ng/ml (4.2)]; (p < 0.05), along with a significant increase in mean serum NO levels in the cardamom group [from 62.9 (18) to 82.5 Mµ (24.6)] compared to the placebo group [70.7 (28) to 72.1 Mµ (25.8)]; (p < 0.001). ConclusionGreen cardamom may have beneficial effects on SBP, NO and hs-CRP levels in patients with T2DM. Improvement in BP and inflammatory markers can help prevent the complications from T2DM including cardiovascular risk in these patients.

Opuntia ficus-indica Alleviates Particulate Matter 10 Plus Diesel Exhaust Particles (PM10D)—Induced Airway Inflammation by Suppressing the Expression of Inflammatory Cytokines and Chemokines

Particulate matter (PM) exposure may cause adverse health effects such as respiratory disorders. We evaluated the protective effects of various Opuntia ficus-indica (OFI) extracts on airway inflammation associated with exposure to PM10D with an aerodynamic diameter <10 μm (PM10) and diesel exhaust particles (DEP). BALB/c mice were exposed to PM10D via intranasal tracheal injection three times over a period of 12 days and various OFI extracts (water, 30% ethanolic, or 50% ethanolic extracts) were administered orally for 12 days. All OFI extracts suppressed neutrophil infiltration and the number of immune cells (CD3+/CD4+, CD3+/CD8+, and Gr-1+/CD11b) in bronchoalveolar lavage fluid (BALF) and lungs. OFI extracts decreased the expression of cytokines and chemokines, including chemokine (C-X-C motif) ligand (CXCL)-1, interleukin (IL)-17, macrophage inflammatory protein-2, tumor necrosis factor (TNF)-α, cyclooxygenase-2, IL-1α, IL-1β, IL-5, IL-6, transient receptor potential cation channel subfamily V member 1, and mucin 5AC, and inhibited IRAK-1, TNF-α, and CXCL-1 localization in BALF and lungs of mice with PM10D-induced airway inflammation. Serum asymmetric and symmetric dimethyl arginine levels were also decreased by OFI extracts treatment. Moreover, all OFI extracts restored histopathological damage in the trachea and lungs of mice with PM10D-induced airway inflammation. These results indicate that OFI extracts may be used to prevent and treat airway inflammation and respiratory diseases.

Serum asymmetric dimethylarginine level correlates with the progression and prognosis of amyotrophic lateral sclerosis.

Background and purpose:The aim was to investigate the association between serum asymmetric dimethylarginine (ADMA) levels and the progression and prognosis of amyotrophic lateral sclerosis (ALS), and to compare cerebrospinal fluid (CSF) and serum ADMA levels with other biomarkers of ALS.MethodsSerum ADMA levels of sporadic ALS patients (n = 68), disease control patients (n = 54) and healthy controls (n = 20) were measured using liquid chromatography tandem mass spectrometry. Correlations of the ADMA level and other markers (nitric oxide and neurofilament light chain levels) were analyzed. Changes in the ALS Functional Rating Scale Revised (ALSFRS‐R) score from the onset of disease (ALSFRS‐R pre‐slope) was used to assess disease progression. Survival was evaluated using the Cox proportional hazards model and Kaplan–Meier analysis.ResultsThe serum ADMA level was substantially higher in patients with ALS than in healthy controls and disease controls. Serum ADMA level correlated with CSF ADMA level (r = 0.591, p < 0.0001) and was independently associated with the ALSFRS‐R pre‐slope (r = 0.505, p < 0.0001). Patients with higher serum ADMA levels had less favorable prognoses. CSF ADMA level significantly correlated with CSF neurofilament light chain level (r = 0.456, p = 0.0002) but not with nitric oxide level (r = 0.194, p = 0.219).ConclusionSerum ADMA level is an independent biomarker of ALS disease progression and prognosis and reflects the degree of motor neuron degeneration.

Association of Endothelin-I and A symmetric Dimethylarginine Levels with Insulin Resistance in Type-2 Diabetes Mellitus Patients

Endothelin-I (ET-I) is one of the potent vasoconstrictors secreted from endothelial cells when needed. Many studies revealed the elevation of serum ET-I with human diabetes and microangiopathies. Since insulin resistance is a case of mixed diabetic and pre-diabetic cases, many risk factors beyond obesity and inflammation are proposed. The current study aims to demonstrate the association between serum ET-I and asymmetric dimethylarginine (ADMA) and insulin resistance in type 2 diabetes mellitus (T2DM). Sera of 73 subjects were enrolled currently (control= 35 subjects, and 38 with T2DM for more than 7 years), aged (40-60) years old, with distinct body mass index (BMI) ≤ 25 for control volunteers and (BMI) ≥ 25 for obesity and diabetes patients. Peripheral serum ET-I and ADMA levels were significantly (P≤ 0.0001) higher in T2DM than the control subjects. Receiver operating characteristic curve analysis regarded ET-I and ADMA as good markers for T2DM disease and insulin resistance, correlations between ET-I and anthropometrics revealed a strong increase of urotensin-II (UII), ADMA, homeostatic model assessment for insulin resistance (HOMA-IR) and hemoglobin A1C (HbA1C) with an increase of ET-I. These results are supported by the data of multiple regression analysis, showing that HOMA-IR, HbA1C, UII, BMI, and mean arterial pressure (MAP) are related to ET-I independently. The endothelin-I and ADMA had a positive relationship with increase insulin resistance and may serve as prognostic and diagnostic clinical biomarkers of insulin resistance. Collectively, Therefore, these measurements could evaluate the incidence of DM, and help to better rise up the knowledge about the progression of DM complications.

Association of mortality and endothelial dysfunction with serum ADMA level in COVID-19 patients.

Objectives:To investigate the role of asymmetric dimethylarginine (ADMA) level in predicting intensive care and mortality in patients affected with coronavirus disease 2019 (COVID-19).Methods:This retrospective, cross-sectional study was conducted at Sakarya University Training and Research Hospital (Sakarya, Turkey) between April and August of 2020. We enrolled patients who were diagnosed with COVID-19 via real-time reverse-transcription polymerase chain reaction and admitted to the intensive care (Severe COVID-19; S-COVID) or non intensive care (Moderate COVID-19; M-COVID). We then analyzed the relationship of the ADMA level with various parameters between S-COVID and M-COVID groups.Results:This study included 87 patients, comprising 43 females and 44 males, with a mean age of 61 and 71.50 years, respectively. The male/female distribution was 22/25 (46.8%/53.2%) in the M-COVID group and 22/18 (55%/45%) in the S-COVID group. The hospitalization time, white blood cell count, neutrophil count, lymphocyte-to-albumin ratio, international normalization ratio, D-dimer, troponin, ferritin, lactate dehydrogenase, C-reactive protein, procalcitonin, erythrocyte sedimentation rate, fibrinogen, lactate, ADMA, and mortality rate were significantly higher (p < 0.05). In contrast, lymphocyte, total cholesterol, high-density lipoprotein, calcium, and albumin values were lower (p < 0.05) in the S-COVID group than in the M-COVID group. While the mortality rate was 55% in S-COVID patients, no mortality was detected in M-COVID patients (p < 0.05). Moreover, ADMA level was 6618 ± 3000 (6400) in S-COVID patients and 5365 ± 3571 (3130) in M-COVID patients, indicating a statistically significant difference (p = 0.012).Conclusion:The asymmetric dimethylarginine level increases in severe outcomes; hence, it can potentially predict severity in patients with COVID-19.

Choroidal thickness and serum asymmetric dimethylarginine levels in patients with systemic sclerosis

Choroidal thickness and serum asymmetric dimethylarginine levels in patients with systemic sclerosis