Asymmetric Dimethylarginine Levels Research Articles

ADMA, neutrophil to lymphocyte, platelet to lymphocyte ratios and phase angle: effects on inflammation and nutrition in hemodialysis patients

Objectives: Neutrophil/lymphocyte ration (NLR) and platelet/lymphocyte ratio (PLR) levels can be used as systemic infallamotory parameters. Asymmetric dimethyl arginine (ADMA) inhibits endothelial nitric oxide synthase. Phase Angle (PhA) is a potential paremeter to screen for inflammatory abnormalities. In present study we aimed to determine the relations between NLR, PLR, ADMA, and PhA in terms of early markers for nutritonal status in addition to their well-known role in inflammation. Methods: A total of 89 patients undergoing maintenance hemodialysis 3 days a week at least 6 months were enrolled. To assess nutritional status, we performed the dietary questionnaire and mini nutritional assessment score (MNAS). ADMA was measured by ELISA. NLR and PLR are calculated from monthly complete blood count tests. Patients were divided into 2 groups accordng to NLR levels as group 1 (NLR≥4.6; n=48) ve and group 2 (NLR<4.6, n=41). Results: The mean ADMA level was 0.03±0.01 µmol/L, the mean PhA was 7.2±1.1º. In subgroup analysis, MNAS, albumin levels and phase angle of patients in group 1 were lower and CRP, PLR, ADMA levels were higher when compared to group 2. In correlation analysis, NLO was positively correlated with PLR, CRP and ADMA however negatively correlated with albumin and PhA levels. In regression analysis, NLR, PLR and ADMA were detected as independent predictors of MNAS. Conclusion: In conclusion our study suggests that NLR, PLR and ADMA are independent predictors for nutritional status and inflammation in patients ongoing hemodialysis.

Laboratory indicators of hemostasis, lipid metabolism and endothelial dysfunction in men aged 18–50 years with different subtypes of ischemic stroke

Objective: to evaluate laboratory parameters of hemostasis, lipid metabolism and endothelial dysfunction and their relationship in men aged 18–50 years with atherothrombotic (ATS), lacunar (LS) and cardioembolic (CES) stroke. Material and methods. The study included 89 men with ATS (n=36), LS (n=34) and CES (n=19). Neuroimaging, ultrasound and laboratory blood serum analyses were performed in all patients. Results. The mean age of the patients was 42.6±5.3 years. The main risk factors for ATS, LS and CES included: arterial hypertension (75; 97.8 and 73.7% of cases, respectively), dyslipidemia (60; 41.3 and 42.1%), tobacco smoking (71.7; 67.4 and 52.6%), regular alcohol consumption (35; 19.6 and 36.8%), obesity (23.3; 8.7 and 15.8 %), diabetes mellitus (8.3; 6.5 and 10.5 %). Lower tissue plasminogen activator levels were found in patients with CES (2.66±1.77 ng/ml) compared to patients with LS (3.38±3.0 ng/ml) and ATS (3.48±2.45 ng/ml). Plasminogen activator inhibitor-1 levels were significantly increased in all stroke subtypes. The mean level of soluble thrombomodulin was highest in patients with LS (100.86±58.22 pg/ml) compared to patients with ATS (96.37±85.71 pg/ml) and CES (75.28±39.36 pg/ml). The level of asymmetric dimethylarginine was higher in patients with ATS (1.46±0.42 μmol/l) and in patients with LS (0.79±0.37 μmol/l), and in patients with CES (0.4±0.13 μmol/l) it was within the reference values. Conclusion. We noted differences in laboratory parameters of the hemostasis, lipid metabolism and endothelial dysfunction in men aged 18–50 years with different stroke subtypes (ATS, LS and CES), as well as clinical and laboratory correlations.

Value of Serum Asymmetric Dimethylarginine (ADMA) As a Novel Biomarker for Uveitis in Behçet’s Disease

ABSTRACT Purpose To evaluate the serum asymmetric dimethylarginine (ADMA) level as a biomarker for uveitis in Behçet’s Disease (BD). Methods In this cross-sectional study, two groups of BD patients were examined: 33 with uveitis and 27 without uveitis. All patients were clinically evaluated, with disease activity measured by Behçet’s Disease Current Activity Form (BDCAF) score. They also underwent thorough ophthalmic evaluation, and routine laboratory investigations, including serum ADMA. Results Patients with BD who experienced active or inactive uveitis had higher levels of serum ADMA compared to those without uveitis. Anterior (ρ = 0.34, p < 0.01), posterior (ρ = 0.3, p < 0.05), and pan uveitis (ρ = 0.35, p < 0.01) were significantly correlated with serum ADMA levels. However, there was no significant correlation between ADMA and other BD manifestations. ROC curve analysis showed that increased serum ADMA levels in BD patients predicted uveitis with a sensitivity of 61.8%, specificity of 96.2%, and AUC of 0.78(95% CI: 0.66–0.9, p < 0.001). Conclusion Serum ADMA level can serve as a novel biomarker of uveitis in BD and its severity with good diagnostic accuracy, regardless of its site or activity.

Asymmetric dimethylarginine correlates with indicators of prethrombotic state in patients with nonvalvular atrial fibrillation.

The mechanism of asymmetric dimethylarginine (ADMA) in thrombosis in patients with nonvalvular atrial fibrillation (NVAF) is still unclear. Our aim was to investigate the relationship between ADMA and indicators of prethrombotic state in NVAF patients and to analyze the predictive role of ADMA in NVAF thrombosis. A total of 192 NVAF patients were continuously selected from January 2023 to October 2023. Plasma ADMA levels were measured by high-performance liquid chromatography. P-selectin (P-sel), von Willebrand factor (vWF), D-dimer (D-D), and plasminogen activator inhibitor-1 (PAI-1) levels were measured by enzyme-linked immunosorbent assay (ELISA). Nitric oxide (NO) levels were measured by the nitrate reductase assay for plasma nitrite/nitrate, then the Griess method (Shanghai Hailian Biotechnology Co., Shanghai, China) was used to calculate plasma NO levels. In our study, ADMA levels were significantly elevated and positively correlated with P-sel, vWF, D-D, and PAI-1, whereas NO levels were significantly negatively correlated with these prethrombotic factors in NVAF. Furthermore, multifactorial logistic regression analysis showed that ADMA and LA diameter were independent predictors of high thrombosis risk (CHA2DS2-VASc ≥2 score) in patients with NVAF. Our findings suggested that ADMA correlated with the prethrombotic state in NVAF and that reduction of ADMA levels in NVAF patients may be a novel therapeutic strategy for thrombosis risk reduction.

Association of Apelin, Chemerin and Omentin Levels with Oxidative Stress Markers in Non-Diabetic and Induced Diabetic Rats

Abstract &#x0D;     Oxidative stress has a significant impact on the etiology of type 1 diabetes mellitus (T1DM). However, associations of adipokines with oxidative stress biomarkers have yet to be investigated. Therefore, the present study aimed to investigate the estimation of serum apelin, chemerin, and omentin levels in induced TIDM and their correlations with oxidative stress markers. The study included sixty male albino rats divided into two groups. The first group (n = 30) was diabetic (TIDM induced with an intraperitoneal injection of 40mg/kg STZ). The non-diabetic control group was the second (n: 30). The enzyme-linked immunosorbent (ELISA) test was used to quantify the serum levels of apelin, chemerin, omentin and asymmetric dimethylarginine (ADMA). Furthermore, blood glucose, lipid profile triglyceride (TG), cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), liver enzymes (alanine aminotransferase (ALT) and aspartate transaminase (AST)), malondialdehyde (MDA) and nitric oxide (NO) parameters were evaluated. Rats with induced TIDM had significantly higher serum levels of apelin, chemerin, omentin, malondialdehyde MDA, ADMA, and NO compared to non-diabetics. According to the coefficient of correlation analysis, the results revealed a positive association between apelin and LDL, ALT, and MDA and a negative correlation between apelin and AST: ALT.  In addition, no correlation was found between apelin and serum levels of glucose, cholesterol, HDL, LDL: HDL TG, TG: HDL, VLDL, AST, creatinine, uric acid, albumin, NO, and ADMA. LDL, ALT, and MDA. Serum chemerin level correlated positively with LD: HDL and ADMA. Also, the plasma level of omentin showed a significant and positive correlation with both TG: HDL and MDA values. In conclusion, the results of this study introduced apelin and chemerin as potential biomarkers for the early detection of diabetes. Elevated serum apelin levels in induced T1DM could provide compensatory action for low insulin levels. While, apelin, chemerin and omentin’s positive correlations with MDA level suggest the potential roles of these adipokines in diabetes-induced complications caused by oxidative stress.

Arginine-NO metabolites are associated with morbidity in single ventricle infants undergoing stage 2 palliation.

Infants with single ventricle heart disease (SVHD) suffer morbidity from insufficient pulmonary blood flow, which may be related to impaired arginine metabolism. No prior study has reported quantitative mapping of arginine metabolites to evaluate the relationship between circulating metabolite levels and outcomes. Prospective cohort study of 75 SVHD cases peri-Stage 2 and 50 healthy controls. We targeted pre- and post-op absolute serum quantification of 9 key members of the arginine metabolism pathway by tandem mass spectrometry. Primary outcomes were length of stay (LOS) and post-Stage 2 hypoxemia. Pre-op cases showed alteration in 6 metabolites including decreased arginine and increased asymmetric dimethyl arginine (ADMA) levels compared to controls. Post-op cases demonstrated decreased arginine and citrulline levels persisting through 48 h. Adjusting for clinical variables, lower pre-op and 2 h post-op concentrations of multiple metabolites, including arginine and citrulline, were associated with longer post-op LOS (p < 0.01). Increased ADMA at 24 h was associated with greater post-op hypoxemia burden (p < 0.05). Arginine metabolism is impaired in interstage SVHD infants and is further deranged following Stage 2 palliation. Patients with greater metabolite alterations experience greater post-op morbidity. Decreased arginine metabolism may be an important driver of pathology in SVHD. Interstage infants with SVHD have significantly altered arginine-nitric oxide metabolism compared to healthy children with deficiency of multiple pathway intermediates persisting through 48 h post-Stage 2 palliation. After controlling for clinical covariates and classic catheterization-derived predictors of Stage 2 readiness, both lower pre-operation and lower post-operation circulating metabolite levels were associated with longer post-Stage 2 LOS while increased post-Stage 2 ADMA concentration was associated with greater post-op hypoxemia. Arginine metabolism mapping offers potential for development using personalized medicine strategies as a biomarker of Stage 2 readiness and therapeutic target to improve pulmonary vascular health in infants with SVHD.

Asymmetric Dimethylarginine and NT-proBNP Levels Provide SynergisticInformation in PulmonaryArterial Hypertension.

Plasma asymmetric dimethylarginine (ADMA) is elevated in pulmonary arterial hypertension (PAH) and is associated with unfavorable outcomes. The aim of this study was to assess changes in ADMA plasma levels for monitoring disease progression and outcomes during PAH-specific therapy. ADMA was measured at baseline and after at least 6months of follow-up using enzyme-linked immunosorbent assay and high-performance liquid chromatography. Changes in ADMA were analyzed in relation to changes in established PAH markers, including hemodynamic status, N-terminal pro-brain natriuretic peptide (NT-proBNP) and risk assessment scores. Impact on survival was assessed using Kaplan-Meier curves and Cox proportional hazards models. Between 2008 and 2019, ADMA samples were collected prospectively from 215 patients with PAH. Change in ADMA plasma level was a predictor of disease progression and survival. ΔADMA (median-0.03μmol/L; 95%CI:-0.145 to 0.0135) was correlated with change in mean pulmonary arterial pressure (P< 0.005; rS=0.287) but was not significantly correlated with ΔNT-proBNP (P=0.056; rS=0.135). Patients with decreased ADMA plasma levels at follow-up had better 3-year and 5-year survival rates (88% and 80%, respectively, vs 72% and 53% in those without decreases in ADMA) (P< 0.005; pulmonary hypertension-related mortality or lung transplantation). Patients with decreases in both ADMA and NT-proBNP had better survival rates compared with patients in whom only 1 parameter improved (P< 0.005). ΔADMA was a significant predictor of survival in Cox regression analysis and also when corrected for ΔNT-proBNP (HRs: 1.27 and 1.35, respectively; P< 0.005). ADMA and NT-proBNP provide synergistic prognostic information for patients with PAH. ADMA could be used as an objective and distinct biomarker for monitoring treatment response in PAH.

CAPE ameliorates vascular damage caused by sepsis

parameters of vascular and oxidative damage caused by sepsis and to evaluated the effects of caffeic acid phenethyl ester (CAPE) on these damages.&#x0D; Materials and Methods: Wistar-Albino male rats were used for this study. Rats were divided into 4 groups (n = 10). Group 1 animals were intraperitoneally (i.p) injected with sterile saline (Control Group). Group 2 animals were i.p injected with lipopolysaccharide (LPS), 20 mg / kg-weight dose (Sepsis Group). Group 3 animals were i.p injected with lipopolysaccharide, 20 mg / kg-weight dose. Immediately after LPS injection, CAPE was i.p injected at single dose, 10 µmol / kg-body weight (Treatment Group). A single dose of CAPE, 10 µmol / kg-body weight / day, was injected i.p to Group 4 animals for 5 days. After 5th day CAPE injection, a single dose of LPS 20 mg / kg-weight was injected (Protective Group). At the 6th hour after the injections applied to all groups, blood sample were taken intracardiac and their serum were separated for the studies. Homocysteine (Hcy), asymmetric dimethyl arginine (ADMA), endothelin-1 (ET-1) and vascular cellular adhesion molecule-1 (VCAM-1) were measured by enzyme-linked immunosorbent assay (ELISA). In addition, the protective and therapeutic effects of CAPE on these parameters was investigated.&#x0D; Results: Control group Hcy, ADMA, ET-1 and VCAM-1 levels were found to be 4.987 ± 0.096 µmol/l, 0.803 ± 0.020 nmol/ml, 21.123 ± 2.575 ng/l, 3.155 ± 0.078 ng/ml, respectively. Sepsis group Hcy, ADMA, ET-1 and VCAM-1 levels were found to be 8.975 ± 0.160 µmol/l, 3.953 ± 0.678 nmol/ml, 52.446 ± 2.546 ng/l, 10.783 ± 1.068 ng/ml, respectively. Treatment group Hcy, ADMA, ET-1 and VCAM-1 levels were found to be 5.286 ± 0.037 µmol/l, 1.304 ± 0.040 nmol/ml, 27.995 ± 1.299 ng/l, 3.72 ± 0.073 ng/ml, respectively. Protective group Hcy, ADMA, ET-1 and VCAM-1 levels were found to be 5.401 ± 0.042 µmol/l, 1.431 ± 0.056 nmol/ml, 32.708 ± 1.326 ng/l, 4.058 ± 0.069 ng/ml, respectively. It was observed that the Hcy, ADMA, ET-1 and VCAM-1 levels of the sepsis group increased significantly compared to the control group (p0.05). It was observed that CAPE treatment significantly decreased these parameters levels. However, the use of CAPE as a protective was not as effective as its treatment effect.&#x0D; Conclusion: Our results demonstrated that sepsis resulted in increase Hcy, ADMA, ET-1, VCAM-1 levels. All these changes indicate that sepsis-mediated vascular damage is increased. Our results demonstrated that CAPE is more effective in preventing sepsis-mediated damages when given as a treatment.

Serum endocan, asymmetric dimethylarginine and lipid profile in children with familial Mediterranean fever.

Familial Mediterranean fever (FMF) is a chronic inflammatory disease, and it is thought that subclinical inflammation persists even when there are no attacks, eventually causing endothelial dysfunction (ED) and atherosclerosis. Limited data are available about serum endocan, asymmetric dimethylarginine (ADMA) and lipid profile in children with FMF, so we aimed to evaluate these markers in children with FMF during the attack-free period. A total of 50 patients diagnosed with FMF and 50 age and sex-matched healthy children were recruited. Serum endocan, ADMA and lipid profiles were measured. Also, atherogenic indices (Castelli's risk indices I and II [CRI I and II], atherogenic index of plasma [AIP] and atherogenic coefficient [AC]) were calculated. Serum endocan, ADMA levels, low-density lipoprotein cholesterol, triglycerides, CRI II and AIP of the FMF patients were significantly higher than controls (p < 0.001). Unlike serum endocan, serum ADMA showed a positive significant correlation with total cholesterol, non-high density lipoprotein cholesterol, CRI I, AIP and AC (p < 0.001, p < 0.001, p = 0.004, p = 0.028, p = 0.004 respectively). Serum ADMA and lipid profile might be used as potential markers for endothelial dysfunction and increased cardiovascular risk in FMF patients. Theoretically, serum ADMA may affect lipid profiles and serum endocan represents an intriguing biomarker related to inflammation. Coexistence of dyslipidemia represents an additional risk factor that contributes to the onset of early atherosclerosis. A few studies investigated the role of changes in lipid profile and lipid ratios in accelerated atherosclerosis pathogenesis in FMF patients. The relationship between colchicine and lipid profile is contradictory. Although colchicine can cause dyslipidemia, it also has anti-atherosclerosis effects. Elevated ADMA level and atherogenic indices in FMF children reflect their potential role in the early detection of cardiovascular affection in FMF patients.

Metabolic Derangement in Non-Alcoholic Fatty Liver Disease: Opportunities for Early Diagnostic and Prognostic Markers.

Non-alcoholic fatty liver disease is a globally prevalent disorder that can rapidly progress if not detected early. Currently, no accepted markers exist for early diagnosis and prognosis of NAFLD. This review describes derangement in major metabolic pathways of lipid, carbohydrate, and amino acids in NAFLD. It suggests that measuring levels of thrombospondin, TyG index, asymmetric dimethylarginine, LAL-A, GLP-1, FGF-21, and GSG index are potential markers for early diagnosis of NAFLD. A single marker may not indicate early NAFLD, and further large-scale studies on correlating levels of Thrombospondin-2, triglyceride-glucose index, and FGF-21 with NAFLD are warranted.

Gut Microbiota and Biomarkers of Endothelial Dysfunction in Cirrhosis.

Our aim was to study the association of endothelial dysfunction biomarkers with cirrhosis manifestations, bacterial translocation, and gut microbiota taxa. The fecal microbiome was assessed using 16S rRNA gene sequencing. Plasma levels of nitrite, big endothelin-1, asymmetric dimethylarginine (ADMA), presepsin, and claudin were measured as biomarkers of endothelial dysfunction, bacterial translocation, and intestinal barrier dysfunction. An echocardiography with simultaneous determination of blood pressure and heart rate was performed to evaluate hemodynamic parameters. Presepsin, claudin 3, nitrite, and ADMA levels were higher in cirrhosis patients than in controls. Elevated nitrite levels were associated with high levels of presepsin and claudin 3, the development of hemodynamic circulation, hypoalbuminemia, grade 2-3 ascites, overt hepatic encephalopathy, high mean pulmonary artery pressure, increased abundance of Proteobacteria and Erysipelatoclostridium, and decreased abundance of Oscillospiraceae, Subdoligranulum, Rikenellaceae, Acidaminococcaceae, Christensenellaceae, and Anaerovoracaceae. Elevated ADMA levels were associated with higher Child-Pugh scores, lower serum sodium levels, hypoalbuminemia, grade 2-3 ascites, milder esophageal varices, overt hepatic encephalopathy, lower mean pulmonary artery pressure, and low abundance of Erysipelotrichia and Erysipelatoclostridiaceae. High big endothelin-1 levels were associated with high levels of presepsin and sodium, low levels of fibrinogen and cholesterol, hypocoagulation, increased Bilophila and Coprobacillus abundances, and decreased Alloprevotella abundance.

Strong Association of Metabolic Parameters with ADMA and VCAM-1 in Normo-Weight Subjects with Metabolic Syndrome.

Metabolic syndrome (MetS) is a risk factor for cardiovascular disease and is linked to obesity. Subjects with MetS who have normo-weight potentially show higher mortality and morbidity. This study aims to reveal the critical essential metabolic parameters associated with endothelial dysfunction in MetS subjects with normo-weight compared to obese. The study was designed using a case-control approach. Ninety-nine MetS subjects (34 Normo-weight and 65 obese) from the urban population were enrolled in this study. The components of MetS are based on NCEP/ATP III criteria. Asymmetric dimethylarginine (ADMA) and vascular cell adhesion molecule 1 (VCAM-1) as markers for endothelial dysfunction were measured in both groups. Fasting blood glucose (FBG) levels were higher in the normo-weight group (143.38 ± 79.8 mg/dL) compared to the obese group (120.89 ± 46.5 mg/dL). High-density lipoprotein cholesterol (HDL-c) levels in the normo-weight group were lower (42.82 ± 10.1 mg/dL) compared to obesity (45.74 ± 9.3 mg/dL), while triacylglycerol (TAG) levels were higher in the obese (197.25 ± 110.5 mg/dL) compared to the normo-weight group (167.03 ± 98.4 mg/dL), although the differences were statistically not significant (all p > 0.05). The difference between ADMA and VCAM-1 levels was statistically not significant in both groups. Correlation between MetS components with endothelial dysfunction parameters shows that metabolic parameters correlate strongly. Interestingly, a stronger correlation between FBG and ADMA was observed in normo-weight (r = 0.519) compared to obese groups (r = 0.445). In addition, TAG consistently shows a significant correlation with ADMA and VCAM-1 in normo-weight groups. Metabolic parameters, especially FBG and TAG, correlate strongly with endothelial dysfunction parameters in normo-weight subjects with metabolic syndrome.

Asymmetric dimethylarginine is associated with the phenomenon of coronary slow flow in patients with nonvalvular atrial fibrillation.

Coronary slow flow phenomena (CSFP) is associated with endothelial and blood component abnormalities in coronary arteries. Asymmetric dimethylarginine (ADMA) can damage the endothelium of the heart or blood vessels in patients with non-valvular atrial fibrillation (NVAF), causing changes in biological medium content. The factors related to the occurrence of CSFP in NVAF patients are currently unknown. Our aim is to analyze the relationship between ADMA and CSFP in NVAF patients. We consecutively enrolled 134 patients diagnosed with NVAF and underwent coronary angiography, 50 control patients without a history of atrial fibrillation and with normal coronary angiographic flow were included at the same time. Based on the corrected TIMI frame count (CTFC), the NVAF patients were categorized into two groups, CTFC≤27 frames and CTFC>27 frames. Plasma ADMA, p-seletion (p-sel), von Willebrand Factor (vWF), D-dimer (D-Di), fibrinogen activator inhibitor-1 (PAI-1) and nitric oxide (NO) were detected by ELISA in the different groups. We counted the general clinical data and analyzed the factors associated with the presence of CSFP on coronary angiography in NVAF patients. We found that plasma ADMA levels were significantly higher among NVAF patients in the CTFC >27 grade group compared with the control or CTFC ≤27 group. In addition, the levels of blood cells and endothelium-related biomarkers (NO, p-seletion, vWF, D-Di, and PAI-1) were significantly altered and correlated with ADMA levels. Multifactorial analysis showed that plasma ADMA [OR (95%CI): 1.65 (1.21-2.43), p<0.001] and left atrial internal diameter [OR (95%CI): 1.04 (1.02, 1.1), p<0.001] could be used as independent risk factors for the development of CSFP in patients with NVAF. The ROC curves of ADMA can predict the development of CSFP in NVAF patients. The minimum diagnostic concentration for the development of CSFP in patients was 2.31 µmol/L. Our study suggests that the high levels of ADMA and left atrial internal diameter in vivo in patients with NVAF can contribute to the development of CSFP. Therefore, aggressive preoperative detection and evaluation of ADMA and left atrial internal diameter can help to deal with the intraoperative presence of CSFP.

Evaluation of Asymmetric Dimethylarginine, Malondialdehyde, and Vitamin Levels of Borderline Personality Disorder Patients With and Without Self-Mutilation.

Believing that oxidative stress may be increased in borderline personality disorder (BPD) patients with self-mutilating behaviors (SMB), we aimed to measure serum asymmetric dimethylarginine (ADMA) and malondialdehyde (MDA) levels in these patients. The study included 60 patients diagnosed with BPD and 30 healthy controls. BPD patients were divided into two groups: 30 female patients with SMB and 30 female patients with no-self-mutilating behavior (NSMB). ADMA, MDA, vitamin A, and vitamin E levels were analyzed. Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) were conducted with the participants. Serum ADMA and MDA levels were higher in SMB and NSMB group compared to control group. Serum vitamin E levels were also lower in the SMB group compared to the control group. Positive correlations were determined between both ADMA and MDA, and between BDI and BAI scores. Also, BAI scores were statistically higher in SMB group compared to NSMB group. It was discovered that levels of ADMA and MDA, which reflected oxidative stress, were elevated in patients with BPD who exhibited SMB. Accordingly, future studies should investigate the role of oxidative stress in a more comprehensive way in terms of the different mechanisms underlying and treatments involved in borderline personality disorder.

Association between Nfr2, HO-1, NF-kB Expression, Plasma ADMA, and Oxidative Stress in Metabolic Syndrome.

Endothelial dysfunction is one of the major factors in the pathogenesis of metabolic syndrome (MetS), and its molecular mechanisms are not completely understood. The present study aimed to examine the connection between nuclear factor2-related factor2 (Nrf2), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), heme oxygenase 1 (HO-1), and plasma asymmetric dimethylarginine (ADMA) and malondialdehyde (MDA) in people with MetS. Participants in the study were as follows: with MetS (n = 30) and without MetS (Control) (n = 14). Expression of Nrf2, NF-kB, and HO-1 was measured in peripheral blood mononuclear cells (PBMCs). Plasma ADMA was determined using the ELISA technique and MDA via the thiobarbituric acid method. Our study showed that mRNA of NF-kB, Nrf2, and HO-1 levels in PBMCs in the MetS group were significantly higher than in the controls by 53%, 130%, and 185% (p < 0.05), respectively. Similarly, elevated levels of MDA (by 78%, p < 0.001) and ADMA (by 18.7%, p < 0.001) were established in the MetS group. Our findings show the importance of transcription factor Nrf2, playing an integral role in the protection of the endothelium, and of NF-κB, a transcription factor mediating the inflammatory response in MetS. Knowledge of complex cellular-molecular mechanisms would allow the use of biomarkers such as Nrf2, NF-kB, HO-1, and ADMA for the assessment of endothelial dysfunction in clinical practice.

Relationships between polymorphisms in keratin genes and Alzheimer’s disease phenotypes.

AbstractBackgroundKeratins are genetically polymorphic and are the largest subset of intermediate filaments. Keratins are also implicated in signaling pathways, inflammation, and disease states. Keratin 9 (KRT9) protein has been identified to have high diagnostic accuracy for Alzheimer’s disease (AD) (PMID:22045497); it was detected in cerebrospinal fluid (CSF) of AD patients but not healthy controls (PMID:24959311). Plasma keratin 9 concentrations also positively correlated with AD‐associated proteins (e.g., apolipoprotein E and tau) in AD patients (PMID:26973255). Post‐translational modification of keratin 83 (KRT83) protein has been associated with serum asymmetric dimethylarginine levels (PMID:34181092), a vascular risk factor implicated in AD. However, our understanding of the role of genetic variation in AD risk is incomplete. Here, we investigate associations between single nucleotide polymorphisms (SNPs) in KRT9, KRT83, and KRT2 (Keratin 2, couples with keratin 9) and AD biomarker phenotypes.MethodIndividuals with mild cognitive impairment (MCI) or AD, and clinically normal controls were selected among ADNI participants. Participants underwent genome‐wide genotyping. Keratin gene variants were identified from the genome‐wide data using dbSNP variant IDs and genotypes were coded additively. Linkage‐disequilibrium‐based clumping on minor allele frequency (MAF) was applied to prioritize more common SNPs. CSF‐Aβ42, ‐tau, and phosphorylated‐tau (p‐tau) levels were quantified via Roche Elecsys immunoassays. Brain‐Aβ deposition was evaluated via normalized PET‐18F‐AV‐45 cortical summary measures (SUVR). White matter hyperintensities (WMH) were obtained from MRI 3D‐T1 and FLAIR sequences via an automated atlas‐based segmentation pipeline. Linear regression models controlling for age, sex, Mini‐Mental State Exam, APOE‐ε4 status, and head size were used to assess association and interaction effects between SNPs and the AD phenotypes in R.ResultAmong included participants (n = 907, 73±7.2 years, 44% female), SNPs in KRT2 (e.g. 3’UTR‐variant rs117041267‐G/A; MAF = 1.4%) and KRT83 (e.g. upstream‐variant KRT83‐rs17119838‐C/T; MAF = 15.6%) were associated with higher CSF‐Aβ42 concentrations (F(2,905) = 4.26,p = 0.014; and F(2,905) = 6.61,p = 0.0014, respectively). Upstream‐variant KRT83‐rs182354391‐C/G (MAF = 1%) showed an association with lower CSF‐tau (F(1,904) = 5.44,p = 0.020). Multiple KRT9 and KRT2 SNPs also showed association with WMH, while KRT2 and KRT83 intron variants showed associations with PET‐Aβ.ConclusionThese candidate gene analyses suggest involvement of multiple keratin family genes in AD, as indicated by differences in amyloid and tau biomarkers, and white matter disease.

The relationship of asymmetric dimethylarginine levels with uncontrolled arterial hypertension and hypertension disease stage

Background: Patients with treatment-resistant hypertension have a worse cardiovascular prognosis compared to those who achieve their target levels of blood pressure (BP). One of biochemical and clinical markers of a decreased response to antihypertensive therapy can be asymmetric dimethylarginine (ADMA), a molecule that reduces formation of nitric oxide and promotes endothelial dysfunction and vasoconstriction.&#x0D; Aim: To assess the status of the nitrogen oxide synthesis system and clinical and laboratory profile in patients, depending on the hypertensive disease stage, who achieved or not achieved their target BP levels during hospitalization.&#x0D; Materials and methods: We performed аn observational retrospective uncontrolled study in a consecutive sample of 192 patients aged 45–65 years who were admitted to the City Clinical Hospital No. 25 (city of Novosibirsk) with a diagnosis of uncomplicated hypertensive crisis. On the day of discharge, the patients were retrospectively divided into 2 groups. Group 1 included patients who achieved their target BP during hospitalization (target BP group, n = 116). Group 2 included patients with uncontrolled hypertension, in whom the administration of three antihypertensive drugs including a diuretic in optimal or maximal tolerated doses did not result in the achievement of the target BP below 140 and/or 90 mm Hg during hospitalization (non-target BP group, n = 76).&#x0D; The following parameters were measured: ADMA, symmetrical dimethylarginine (SDMA), N-monomethyl-L-arginine (NMMA), and total nitric oxide.&#x0D; Results: Serum ADMA concentrations (Me [Q25%; Q75%] were increasing with the stage of hypertension: stage I, 0.75 µmol/L [0.66; 0.78], stage II, 1.14 µmol/L [0.87; 1.39], stage III, 1.38 µmol/L [1.22; 1.49] (p 0.0001, Kruskal-Wallis test). In the pairwise comparison, the difference between all these subgroups was significant at p 0.01. In the patients with uncontrolled arterial hypertension ADMA levels were increased compared to those in the target BP group: 1.2 µmol/L [0.99; 1.47] vs 1.07 [0.79; 1.34] µmol/L (p = 0.002). The proportion of patients with type 2 diabetes mellitus among those with uncontrolled arterial hypertension was 31.2% (24/76), while in the target BP group there were only 3.5% of such patients (4/116) (odds ratio 12.57, 95% confidence interval 4.15–38.05; p = 0.00001).&#x0D; Conclusion: ADMA measurement may help identify patients with a potential poor response to antihypertensive therapy. This should be taken into account when choosing a treatment regimen and BP monitoring. In addition, ADMA seems to be a promising target for the development of new drug classes.

Successful endodontic treatment reduces serum levels of cardiovascular disease risk biomarkers-high-sensitivity C-reactive protein, asymmetric dimethylarginine, and matrix metalloprotease-2.

To investigate serum biomarkers of inflammation 2 years following non-surgical root canal re-treatment (Re-RCT) and peri-apical surgery (PS). The results were correlated with signs and symptoms, treatment outcome, metabolic syndrome factors, infection with severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 (COVID-19) infection and COVID-19 vaccination. Subjects from our previous study were recalled for 2 years post-treatment follow-up. Changes to the patient's history (medical, dental, social) were noted. Periapical health of the treated teeth was examined both clinically and radiographically. Blood pressure, fasting HbA1C and low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides and total cholesterol (TC) levels were measured. Serum inflammatory marker levels were assayed using a Bio-Rad Bio-Plex 200 analyser and values at different time points within the same group were compared using a Wilcoxon signed-rank test and differences between groups with a Mann-Whitney test. Linear associations were tested using Pearson's correlations. The recall percentage at 2 years was 56.9% (n = 37), with a 100% radiographic success rate using periapical radiographs. In total, 21 cases (56.8%) were completely healed, and 16 cases (43.2%) were healing. Higher matrix metalloprotease 2 (MMP2) levels were present in the healing group compared to the healed group. Serum levels of high-sensitivity C-reactive protein (hs-CRP), asymmetric dimethylarginine (ADMA) and MMP-2 were significantly reduced (p ≤ .001) whereas other biomarkers showed significant increases at 2 year compared to pre-operative levels, while FGF-23 and ICAM-1 were not significantly increased. HbA1C (p = .015), TC (p = .003), LDL (p = .003) and HDL (p = .003) reduced significantly at 2 years post-treatment compared to their preoperative levels. COVID infection showed a significant association with MMP-9 (p = .048). hs-CRP, ADMA and MMP-2 can be regarded as prognostic biomarkers of successful Re-RCT and PS as they reduced at 2 year recall in cases which showed evidence of clinical and radiographic success. The successful treatment of chronic apical periodontitis is correlated with improvements in metabolic syndrome indicators, better glycemic control, and reduction at 2 year of some systemic inflammatory markers which are related to risks of cardiovascular disease events.

Klotho and lean mass as novel cardiovascular risk factors in hemodialysis patients.

Patients with chronic kidney disease (CKD) present a higher risk of cardiovascular (CV) morbidity and mortality compared with the general population. While there are several well-established traditional CV risk factors, few studies have addressed novel potential risk factors such as α-Klotho, asymmetric dimethylarginine (ADMA) and lean mass. This was an observational, prospective, single-center, cohort study that included prevalent hemodialysis (online hemodiafiltration) adult patients. By univariate logistic regression models, univariate and multivariate Cox proportional hazards models, and Kaplan-Meier analysis, we evaluated the association between the levels of α-Klotho, ADMA and lean mass, with the risk of peripheral vascular disease (PVD), CV events and all-cause mortality in these patients. A total of 200 HD patients was included. We found that increased levels of log-α-Klotho were significantly associated with decreased odds of both PVD [odds ratio (OR) 0.521, 95% confidence interval (CI) 0.270-0.954, P=.034] and CV events (OR 0.415, 95% CI 0.203-0.790, P=.01), whereas increased levels of log-ADMA were only significantly associated with increased odds of PVD (OR 13.482, 95% CI 5.055-41.606, P<.001). We also found that the levels of log-α-Klotho (HR 0.357, 95% CI 0.140-0.906, P<.05) and lean mass (HR 0.187, 95% CI 0.042-0.829, P<.05), but not log-ADMA, were significantly associated with the risk of all-cause mortality, even after adjusting for possible confounding variables. Novel long-term clinical associations were generated that support α-Klotho and lean mass as novel CV risk factors in hemodialysis patients.

DDAH1 Protects against Cardiotoxin-Induced Muscle Injury and Regeneration.

Nitric oxide (NO) is an important biological signaling molecule affecting muscle regeneration. The activity of NO synthase (NOS) is regulated by dimethylarginine dimethylaminohydrolase 1 (DDAH1) through degradation of the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA). To investigate the role of DDAH1 in muscle injury and regeneration, muscle-specific Ddah1-knockout mice (Ddah1MKO) and their littermates (Ddah1f/f) were used to examine the progress of cardiotoxin (CTX)-induced muscle injury and subsequent muscle regeneration. After CTX injection, Ddah1MKO mice developed more severe muscle injury than Ddah1f/f mice. Muscle regeneration was also delayed in Ddah1MKO mice on Day 5 after CTX injection. These phenomena were associated with higher serum ADMA and LDH levels as well as a great induction of inflammatory response, oxidative stress and cell apoptosis in the gastrocnemius (GA) muscle of Ddah1MKO mice. In the GA muscle of CTX-treated mice, Ddah1 deficiency decreased the protein expression of M-cadherin, myogenin, Bcl-2, peroxiredoxin 3 (PRDX3) and PRDX5, and increased the protein expression of MyoD, TNFα, Il-6, iNOS and Bax. In summary, our data suggest that DDAH1 exerts a protective role in muscle injury and regeneration.