Analyzing the local pericardial fluid (PF) surrounding the heart can provide insights into the function of myocardial and pericardial epithelial cells. Kynurenine (KYN) metabolites have been associated with endothelial dysfunction and the progression of atherosclerosis. This study investigated the relationship between KYN pathway metabolites in serum and PF and the severity of coronary atherosclerosis, as assessed by the Syntax Score (SS). The study involved 101 patients (mean age: 60 years). Of the participants, 17% were female. KYN and its metabolite levels were measured using API SCIEX 3200 LC-MS/MS methods. Statistical analysis was performed using IBM SPSS 25.0. The mean serum levels of tryptophan (TRP), 3-hydroxykynurenine (3-HK), and 3-hydroxyanthranilic acid were significantly higher (p < 0.01) when compared to the mean PF levels. In the SS-low group, PF IDO activity was significantly higher than serum IDO activity (p = 0.040). In the SS-high group, PF IDO activity was significantly higher than serum IDO activity (p = 0.002). The mean 3-HK measurements showed significant differences between the SS groups (p < 0.05). In this study, higher IDO enzyme activity in the PF compared to systemic circulation suggests the presence of inflammatory activity in the pericardial endothelial cells. This research aimed to uncover the role of amino acid metabolism, which is poorly understood in atherosclerosis. Specifically, 3-HK, a metabolite from the KYN pathway, may contribute to the development of atherosclerosis. These findings indicate that localized kynurenine pathway activation in the PF may contribute to coronary atherosclerosis, highlighting its potential as a biomarker or therapeutic target.

BACKGROUND . Type 2 Diabetes Mellitus (T2DM) is a primary public health concern globally, characterized by chronic hyperglycemia, insulin resistance, impaired beta-cell function. Endothelial dysfunction is a hallmark of diabetes and is exacerbated by hyperlipidemia. AIM . This study investigates the impact of hyperlipidemia on nitric oxide synthesis, arginine metabolism, and vascular health markers in T2DM. MATERIALS AND METHODS . A total of 120 participants were included in this cross-sectional, comparative study. Serum methylarginine derivatives (Asymmetric dimethyl arginine (ADMA), Symmetric dimethyl arginine (SDMA), L-N Mono-methylarginine (L-NMMA) and related metabolites (arginine, homoarginine, citrulline, ornithine) levels were measured in three groups: diabetes with hyperlipidemia (DM-HL), diabetes with normolipidemia (DM-NL), and healthy controls (HC) using API SCIEX 3200 LC-MS/MS methods. Statistical comparisons between groups were performed using IBM SPSS 26.0 to assess the influence of hyperlipidemia on these markers. RESULTS . ADMA and SDMA levels were significantly elevated in DM-HL group compared to DM-NL and HC (p=0.001, p=0.000 respectively), indicating increased endothelial dysfunction and potential dyslipidemia-induced renal or vascular impairment. Reduced arginine and homoarginine levels in diabetic groups suggest impaired nitric oxide synthesis and altered urea cycle function (p=0.013, p=0.000 respectively). Notably, the DM-HL group exhibited significantly higher L-NMMA levels (p=0.001). It disrupted metabolic ratios (e.g., SDMA/ADMA, arginine/ADMA, and homoarginine/ADMA), reflecting enhanced nitric oxide inhibition and reduced bioavailability. Hyperlipidemia significantly exacerbated these disruptions, as evidenced by altered citrulline/arginine and citrulline/ADMA ratios, underscoring its additive impact on endothelial dysfunction. CONCLUSIONS . Hyperlipidemia amplifies the adverse effects of diabetes on endothelial function by exacerbating nitric oxide inhibition, oxidative stress, and arginine metabolism dysregulation. Key biomarkers and metabolic ratios, particularly ADMA and SDMA-related indices, provide valuable insights into cardiovascular risk in this population. Therapeutic strategies targeting lipid management, arginine supplementation, and ADMA reduction could improve vascular health and mitigate cardiovascular complications in DM-HL.

Accurate measurement of urine creatinine is essential for evaluating renal function. Although the Jaffe and enzymatic methods are routinely applied in clinical laboratories, various urinary compounds can interfere with these assays. This study investigated the effects of hemoglobin and protein positivity on creatinine measurement and partially validated a mass spectrometric (LC–MS/MS) procedure. Urine samples from 136 participants were categorized based on dipstick results into three groups: negative (n = 55), hemoglobin-positive (n = 51), and protein-positive (n = 30). Creatinine concentrations were measured using Jaffe and enzymatic methods on an Architect c16000 analyzer and by LC–MS/MS on an API 3200 system. The LC–MS/MS method demonstrated linearity between 3–350 mg/dL, intra- and inter-assay coefficients of variation of 3.2–3.8% and 1.9–2.9%, and bias values ranging from 1.1% to 18.2%. Correlations among LC–MS/MS, enzymatic, and Jaffe methods ranged from 0.981 to 0.998. Bland–Altman analysis showed mean absolute biases of 0.06 to 17.33 mg/dL (1.48–19.42%) in controls, 1.44 to 4.78 mg/dL (0.79–9.59%) in hemoglobin-positive samples, and 2.18 to 9.87 mg/dL (0.52–14.39%) in protein-positive samples. Regression analysis showed slopes closer to unity in hemoglobin- and protein-positive samples compared to controls, likely reflecting higher creatinine concentrations in these groups. Despite this apparent improvement, bias values increased, particularly in protein-positive samples. Both routine methods showed acceptable agreement with LC–MS/MS, while the enzymatic method demonstrated slightly closer agreement under these conditions. LC–MS/MS maintained highest analytical specificity. These findings highlight the importance of method selection for reliable interpretation of renal function, especially in patients presenting with hematuria or proteinuria.