Covalent post-synthetic modification of MOFs as a fluorescent sensor for the efficient detection of the biomarker of cystinuria.

Cystinuria is a genetic disorder, and in severe cases, it might lead to kidney failure. As an important biomarker for cystinuria, the level of arginine (Arg) in urine is a vital indicator for cystinuria screening. Therefore, it is urgently needed to detect Arg with high selectivity and sensitivity. In this work, a boric acid functionalized Zr-based metal-organic framework UiO-PhbA is prepared by grafting phenylboronic acid on UiO-66-NH2 through a Schiff base reaction using a covalent post-synthesis modification (CPSM) strategy. The prepared UiO-PhbA exhibits a sensitive and specific fluorescence "turn-on" response to Arg and can be exploited to detect Arg in human serum and urine samples with a broad linear range of 0.6-350 µM and low limit of detection (LOD) of 18.45 nM. This study provides a new and reliable rapid screening protocol for sulfite oxidase deficiency-related diseases.

Associations of Plasma Metabolites With Risks of Incident Stroke and Its Subtypes in Chinese Adults.

BACKGROUND: Metabolomics studies have identified various metabolic markers associated with stroke risk, yet much uncertainty persists regarding heterogeneity in these associations between different stroke subtypes. We aimed to examine metabolic profiles associated with incident stroke and its subtypes in Chinese adults. METHODS AND RESULTS: We performed a nested case-control study within the Dongfeng-Tongji cohort, including 1029 and 266 incident cases of ischemic stroke (IS) and hemorrhagic stroke (HS), respectively, with a mean follow-up period of 6.1±2.3 years. Fifty-five metabolites in fasting plasma were measured by ultra-high-performance liquid chromatography-mass spectrometry. We examined the associations of metabolites with the risks of total stroke, IS, and HS, with a focus on the comparison of associations of plasma metabolite with IS and HS, using conditional logistic regression. We found that increased levels of asymmetrical/symmetrical dimethylarginine and glutamate were significantly associated with elevated risk of total stroke (odds ratios and 95%, 1.20 [1.08-1.34] and 1.22 [1.09-1.36], respectively; both Benjamini-Hochberg-adjusted P <0.05). When examining stroke subtypes, asymmetrical/symmetrical dimethylarginine was nominally associated with both IS and HS (odds ratios [95% CIs]: 1.16 [1.03-1.31] and 1.39 [1.07-1.81], respectively), while glutamate was associated with only IS (odds ratios [95% CI]: 1.26 [1.11-1.43]). The associations of glutamate with IS risk were significantly stronger among participants with hypertension and diabetes than among those without these diseases (both P for interaction <0.05). CONCLUSIONS: This study validated the positive associations of asymmetrical/symmetrical dimethylarginine and glutamate with stroke risk, mainly that of IS, in a Chinese population, and revealed a novel unanimous association of with both IS and HS. Our findings provided potential intervention targets for stroke prevention.

Evaluation of endothelial glycocalyx injury biomarkers in feline hemotropic mycoplasmosis.

The present study aimed to investigate endothelial glycocalyx (eGCx) damage in cats with feline hemotropic mycoplasmosis caused by Mycoplasma haemofelis using selected biomarkers and to determine the diagnostic and prognostic significance of these biomarkers. The study included 25 cats with feline hemotropic mycoplasmosis and 10 healthy cats. Clinical examination, blood gas analysis, complete blood count, and biochemical analysis were performed. Hemotropic mycoplasmosis diagnosed by microscopic examination and molecularly confirmed by PCR targeting the Mycoplasma haemofelis 16s rRNA gene. To evaluate endothelial glycocalyx damage, syndecan-1, endothelin-1 (ET-1), asymmetric dimethylarginine (ADMA), and vascular endothelial growth factor-A (VEGF-A) concentrations were measured using cat-specific commercial ELISA kits. Of the cats with feline hemotropic mycoplasmosis, 14 (56%) survived and 11 (44%) died. While syndecan-1 and ET-1 concentrations were significantly higher in cats with hemotropic mycoplasmosis compared to the control group (p < 0.001), no statistically significant difference was found for ADMA and VEGF-A concentrations (p > 0.05). Endothelial glycocalyx biomarkers showed significant correlations with each other and with hematological parameters (p < 0.01). The results of the ROC analysis showed that ET-1 with area under the curve (AUC) of 0.821 (p < 0.01) and VEGF-A with AUC of 0.805 (p < 0.010) were found to be significant prognostic indicators. In conclusion, this study demonstrated that serum syndecan-1 and ET-1 can be used as diagnostic and serum ET-1 and VEGF-A as prognostic biomarkers in cats with hemotropic mycoplasmosis. Our results indicate the development of eGCx damage in feline hemotropic mycoplasmosis and suggest that glycocalyx disruption may contribute to the pathogenesis of the disease.

Levels of asymmetric dimethylarginine in plasma and aqueous humor: a key risk factor for the severity of fibrovascular proliferation in proliferative diabetic retinopathy.

Introduction: Proliferative diabetic retinopathy (PDR) is a common diabetes complication, significantly impacting vision and quality of life. Previous studies have suggested a potential link between arginine pathway metabolites and diabetic retinopathy (DR). Connective tissue growth factor (CTGF) plays a role in the occurrence and development of fibrovascular proliferation (FVP) in PDR patients. However, the relationship between arginine pathway metabolites and FVP in PDR remains undefined. This study aimed to explore the correlation between four arginine pathway metabolites (arginine, asymmetric dimethylarginine[ADMA], ornithine, and citrulline) and the severity of FVP in PDR patients. Methods: In this study, plasma and aqueous humor samples were respectively collected from 30 patients with age-related cataracts without diabetes mellitus (DM) and from 85 PDR patients. The PDR patients were categorized as mild-to-moderate or severe based on the severity of fundal FVP. The study used Kruskal-Wallis test to compare arginine, ADMA, ornithine, and citrulline levels across three groups. Binary logistic regression identified risk factors for severe PDR. Spearman correlation analysis assessed associations between plasma and aqueous humor metabolite levels, and between ADMA and CTGF levels in aqueous humor among PDR patients. Results: ADMA levels in the aqueous humor were significantly greater in patients with severe PDR than in those with mild-to-moderate PDR(P=0.0004). However, the plasma and aqueous humor levels of arginine, ornithine, and citrulline did not significantly differ between mild-to-moderate PDR patients and severe PDR patients (P>0.05). Binary logistic regression analysis indicated that the plasma (P=0.01) and aqueous humor (P=0.006) ADMA levels in PDR patients were risk factors for severe PDR. Furthermore, significant correlations were found between plasma and aqueous humor ADMA levels (r=0.263, P=0.015) and between aqueous humor ADMA and CTGF levels (r=0.837, P<0.001). Conclusion: Elevated ADMA levels in plasma and aqueous humor positively correlate with the severity of FVP in PDR, indicating ADMA as a risk factor for severe PDR.

A panel of four plasma amino acids is a promising biomarker for newly diagnosed bladder cancer.

BACKGROUND: Metastasis and recurrence are the main causes of death in post-operative bladder cancer (BC), emphasizing the importance of exploring early-stage diagnostic markers. Serum biomarkers constitute a promising diagnostic approach for asymptomatic stage cancer as they are non-invasive, have high accuracy and low cost. AIMS: To correlate concentrations of plasma amino acids with BC progression to assess their utility as an early-stage diagnostic. METHODS: Newly diagnosed BC patients (n = 95) and normal controls (n = 96) were recruited during the period from 1 December 2018 to 30 December 2020. General and food frequency questionnaires established their basic information and dietary intake data. Venous blood samples were collected from fasting subjects and used to detect levels of plasma amino acids by liquid chromatography-mass spectrometry. Verification was performed on the GSE13507 transcriptome gene expression matrix of BC from Gene Expression Omnibus (GEO) database. RESULTS: Eleven amino acids have been identified as altered in the plasma of newly diagnosed BC patients compared to controls (P < 0.05). Adjusted by gender, education, smoking and other factors, plasma ornithine level (OR = 0.256, 95% CI: 0.104-0.630) is a protective factor for BC, plasma levels of methionine (OR = 3.460, 95% CI: 1.384-8.651), arginine (OR = 3.851, 95% CI: 1.542-9.616), and glutamate (OR = 3.813, 95% CI: 1.543-9.419) are all risk factors for BC. ROC analysis demonstrated that the combination of plasma ornithine, methionine, arginine and glutamate could accurately diagnose BC (AUC = 0.84, 95% CI: 0.747-0.833). In addition, the mRNA level of arginase 1 was decreased (P < 0.05), while the inducible nitric oxide synthase was increased significantly, which may be linked with the disturbance of arginine metabolism in BC patients. Further analysis of GEO database confirmed the role of arginine metabolism. CONCLUSION: A biomarker panel containing four amino acids may provide a feasible strategy for the early diagnosis of BC. However, further validation is required through prospective studies.

Angiogenesis-associated pathways play critical roles in neonatal sepsis outcomes.

Neonatal sepsis is a major cause of childhood mortality. Limited diagnostic tools and mechanistic insights have hampered our abilities to develop prophylactic or therapeutic interventions. Biomarkers in human neonatal sepsis have been repeatedly identified as associated with dysregulation of angiopoietin signaling and altered arachidonic acid metabolism. We here provide the mechanistic evidence in support of the relevance for these observations. Angiopoetin-1 (Ang-1), which promotes vascular integrity, was decreased in blood plasma of human and murine septic newborns. In preclinical models, administration of Ang-1 provided prophylactic protection from septic death. Arachidonic acid metabolism appears to be functionally connected to Ang-1 via reactive oxygen species (ROS) with a direct role of nitric oxide (NO). Strengthening this intersection via oral administration of arachidonic acid and/or the NO donor L-arginine provided prophylactic as well as therapeutic protection from septic death while also increasing plasma Ang-1 levels among septic newborns. Our data highlight that targeting angiogenesis-associated pathways with interventions that increase Ang-1 activity directly or indirectly through ROS/eNOS provide promising avenues to prevent and/or treat severe neonatal sepsis.

Early and late-onset preeclampsia: effects of DDAH2 polymorphisms on ADMA levels and association with DDAH2 haplotypes.

Objective: To examine whether the DDAH2 promoter polymorphisms -1415G/A (rs2272592), -1151A/C (rs805304) and -449G/C (rs805305), and their haplotypes, are associated with PE compared with normotensive pregnant women, and whether they affect ADMA levels in these groups. Methods: A total of 208 pregnant women were included in the study and classified as early-onset (N=57) or late-onset PE (N =49), and as normotensive pregnant women (N = 102). Results: Pregnant with early-onset PE carrying the GC and GG genotypes for the DDAH2 -449G/C polymorphism had increased ADMA levels (P=0.01). No association of DDAH2 polymorphisms with PE in single-locus analysis was found. However, the G-C-G haplotype was associated with the risk for late-onset PE. Conclusion: It is suggested that DDAH2 polymorphisms could affect ADMA levels in PE, and that DDAH2 haplotypes may affect the risk for PE.

High ADMA Is Associated with Worse Health Profile in Heart Failure Patients Hospitalized for Episodes of Acute Decompensation.

Background and Objectives: episodes of acute decompensation in chronic heart failure (ADHF), a common health problem for the growing elderly population, pose a significant socio-economic burden on the public health systems. Limited knowledge is available on both the endothelial function in and the cardio-metabolic health profile of old adults hospitalized due to ADHF. This study aimed to investigate the connection between asymmetric dimethylarginine (ADMA)-a potent inhibitor of nitric oxide-and key health biomarkers in this category of high-risk patients. Materials and Methods: this pilot study included 83 individuals with a known ADHF history who were admitted to the ICU due to acute cardiac decompensation. Selected cardiovascular, metabolic, haemogram, renal, and liver parameters were measured at admission to the ICU. Key renal function indicators (serum creatinine, sodium, and potassium) were determined again at discharge. These parameters were compared between patients stratified by median ADMA (114 ng/mL). Results: high ADMA patients showed a significantly higher incidence of ischemic cardiomyopathy and longer length of hospital stay compared to those with low ADMA subjects. These individuals exhibited significantly higher urea at admission and creatinine at discharge, indicating poorer renal function. Moreover, their lipid profile was less favorable, with significantly elevated levels of total cholesterol and HDL. However, no significant inter-group differences were observed for the other parameters measured. Conclusions: the present findings disclose multidimensional, adverse ADMA-related changes in the health risk profile of patients with chronic heart failure hospitalized due to recurrent decompensation episodes.

Effect of medium cut-off membranes on Pentosidine and N-(carboxymethyl) lysine levels in uncontrolled diabetic hemodialysis patients.

INTRODUCTION: Patients on hemodialysis, especially with diabetes, face elevated cardiovascular events. A major contributor to complications associated with diabetes is advanced glycation end products (AGEs). Removing these compounds is challenging in traditional hemodialysis. Medium-cut-off (MCO) membranes potentially remove toxins without significant albumin loss. This study explored how MCO membranes impact AGEs levels in uncontrolled diabetic patients undergoing hemodialysis. METHODS: Sixteen patients received MCO membrane dialysis, while others used high-flux (HF) membranes. After 12 sessions, the dialyzers were switched, totaling 24 sessions. Blood samples at trial initiation (T0), session 12 (T1) and session 24 (T2) tested for CML, Pentosidine, laboratory parameters. RESULTS: Switching dialyzers showed increased albumin with MCO-to-HF and decreased with HF-to-MCO, albeit nonsignificant (p = 0.5/p = 0.1). Patients on MCO had lower albumin levels than HF (p = 0.03/p = 0.6, respectively). Hemodialysis with MCO demonstrated lower levels of CML/Pentosidine compared to HF (p = 0.09/p = 0.9 for CML; p = 0.04/p = 0.3 for Pentosidine). Transitioning to HF led to elevated levels (p = 0.4/p = 0.09 for CML; p = 0.3/p = 0.07 for Pentosidine). CONCLUSION: MCO dialysis in diabetic individuals notably reduces AGE levels.

The correlation between vitamin D3 and arginine metabolism levels in newborns with amino acid metabolism disorders.

This study aimed to explore the correlation between vitamin D3 and arginine (Arg) metabolism indicators in newborns with amino acid metabolism disorders. Based on clinical data, 30 newborns with amino acid metabolism diseases admitted to Shijiazhuang Fourth Hospital from June 2021 to June 2022 were selected as the disease group, and 30 healthy newborns from the same period were selected as the healthy group. After enrollment, blood samples were collected to measure the levels of Arg, Glycine (Gly), and vitamin D3 levels. The levels of Arg metabolism indicators and vitamin D3 levels in the 2 groups and the correlation between vitamin D3 levels and Arg metabolism indicators in the affected group were analyzed. The Arg level in the diseased group was higher than that in the healthy group, whereas the Gly and vitamin D3 levels were lower than those in the healthy group (P < .05). There was a significant negative correlation between vitamin D3 and Arg levels in the affected group, and a significant positive correlation with Gly levels (P < .05). Newborns with amino acid metabolism disorders have abnormally high Arg levels, significantly reduced Gly levels, and significantly decreased vitamin D3 levels. The degree of decline was closely related to the levels of indicators of Arg metabolism. Vitamin D3 supplementation can improve the Arg metabolism status of newborns with amino acid metabolism disorders.

Asymmetric and symmetric dimethylarginine as markers of endothelial dysfunction in cerebrovascular disease: A prospective study.

BACKGROUND AND AIM: Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) have been proposed as mediators of endothelial dysfunction. In this study, we aimed to investigate the diagnostic and prognostic role of ADMA and SDMA in acute cerebrovascular disease. METHODS AND RESULTS: A prospective case-control study was performed, enrolling 48 patients affected by ischemic stroke with no cardioembolic origin, 20 patients affected by TIA, 40 subjects at high cardiovascular risk and 68 healthy subjects. ADMA levels were significantly lower in high-risk subjects (18.85 [11.78-22.83] µmol/L) than in patients with brain ischemic event, both transient (25.70 [13.15-40.20] µmol/L; p = 0.032) and permanent (24.50 [18.0-41.33] µmol/L; p = 0.001). SDMA levels were different not only between high-risk subjects and ischemic patients, but also between TIA and stroke patients, reaching higher levels in TIA group and lower levels in stroke group (1.15 [0.90-2.0] vs 0.68 [0.30-1.07] µmol/L; p < 0.001). SDMA was also correlated with short-term prognosis, with lower levels in case of adverse clinical course, evaluated by type of discharge (p = 0.009) and need of prolonged rehabilitation (p = 0.042). CONCLUSIONS: The present study highlights the relationship between l-arginine, ADMA, SDMA and acute cerebrovascular events. Therefore, our results suggested a potential role of SDMA as a specific marker of transient ischemic damage and as a short-term positive prognostic marker.

Triglycerides: A Sensitizer but Not a Trigger for Hypertriglyceridemic Acute Pancreatitis.

BACKGROUND: The incidence of hypertriglyceridemic acute pancreatitis (HTG-AP) is increasing. Although the guideline defines the diagnostic criteria as triglyceride (TG) greater than 11.3 mmol/L, there is actually no specific threshold. Many people with hypertriglyceridemia (HTG) or obvious chyloid blood do not develop acute pancreatitis (AP). AIMS: To explore the role of HTG in the pathogenesis of AP. METHODS: Thirty-six male SD rats were randomly assigned into normal control, AP, HTG, HTG-AP, low-dose fenofibrate and high-dose fenofibrate groups. Serum indices and cytokine levels in serum, and pathological changes in pancreatic tissues were observed. The expression levels of TLR4 and NF-κBp65 in pancreatic tissues were detected by immunohistochemistry and Western blot. RESULTS: In normal rats, HTG alone did not induce AP. However, after establishing the HTG-AP model with Poloxam 407 and L-arginine, serum-free fatty acid and TG levels were positively correlated with the levels of lipase, amylase, IL-1ß, IL-6, pancreatic inflammation scores, and the expressions of TLR4 and NF-κBp65 (all P < 0.001). Expressions of TLR4 and NF-κBp65 were significantly increased in the pancreatic tissues of HTG-AP rats. Fenofibrate effectively decreased TG levels in HTG-AP rats and reduced the expression of TLR4 and NF-κBp65 (all P < 0.001). CONCLUSIONS: HTG does not directly cause AP, but rather increases the susceptibility to AP or aggravates the inflammatory response. It is more like a sensitizer of inflammation rather than an activator.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Impact of Immunonutrition on Nutritional Status in Patients Undergoing Colorectal Cancer Surgery: A Randomized Controlled Clinical Trial.

This study aimed to investigate the additional effects of perioperative immunonutrition (IMN) compared with preoperative immunonutrition (IMN) on anthropometric, nutritional, and biochemical parameters, hospital stay and postoperative complications in patients with colorectal cancer. Oral supplementation enriched with arginine, omega-3 fatty acids, and dietary nucleotides was given to 25 patients before and after the operation (Group 2); 25 patients received the same formula before surgery and standard isocaloric nutrition following the operation (Group 1). Postoperative body weight, body mass index (BMI), and middle upper arm circumference (MUAC) of Group 1 decreased more than Group 2 during follow-up (p < 0.05). The biochemical parameters, C-reactive protein (CRP), aspartate aminotransferase (AST) and fasting plasma glucose (FPG) were higher, and albumin was lower than the baseline in Group 1 compared to Group 2 (p < 0.05). There was a negative correlation between CRP and Nutrition Risk Screening (NRS) 2002 scores, and prealbumin and NRS 2002 scores had a positive correlation (p = 0.007, r = 0.384; p = 0.012, r = 0.352). There was no difference in hospital stay and postoperative complications between the groups (p > 0.05). Perioperative immunonutrition, compared to preoperative immunonutrition, can be used as a positive and effective approach in improving some anthropometric measurements and biochemical parameters in patients undergoing colorectal cancer surgery.

Asymmetric Dimethylarginine and NT-proBNP Levels Provide Synergistic Information in Pulmonary Arterial Hypertension.

BACKGROUND: Plasma asymmetric dimethylarginine (ADMA) is elevated in pulmonary arterial hypertension (PAH) and is associated with unfavorable outcomes. OBJECTIVES: The aim of this study was to assess changes in ADMA plasma levels for monitoring disease progression and outcomes during PAH-specific therapy. METHODS: ADMA was measured at baseline and after at least 6 months 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. RESULTS: 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 -0.03 µmol/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). CONCLUSIONS: 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.

Description of serum symmetric dimethylarginine concentration and of urinary SDS-AGE pattern in dogs with ACTH dependent hyperadrenocorticism.

Serum symmetric dimethylarginine (SDMA) and patterns of urinary protein separated by sodium dodecyl sulfate agarose gel electrophoresis (SDS-AGE) have not been investigated as biomarkers in dogs with ACTH-dependent hyperadrenocorticism (ADHAC). This exploratory prospective study aimed to evaluate SDMA, serum creatinine (sCR), and SDS-AGE in dogs with ADHAC with and without proteinuria (ADHAC-P and ADHAC-nP, respectively). Thirty-five pet dogs classified as ADHAC-P (n=16), ADHAC-nP (n=6) and healthy (n=13) were included. Renal biomarkers were evaluated in all dogs at diagnosis. Baseline concentration of SDMA was not significantly different between the three groups (P = 0.15) whereas sCr was significantly lower in dogs in ADHAC dogs compared to healthy dogs (88.0 µmol/L [70.4-132.6; 79.2-114.4]) whether they had proteinuria or not (P = 0.014 and 0.002, respectively). However, baseline concentrations of sCr and SDMA were not significantly different between dogs with ADHAC-P dogs (SDMA, 8 µg/dL [5-12; 7-9]; sCr, 57.2 µmol/L [35.2-212.2; 52.8-92.4]) and ADHAC-nP dogs (SDMA, 8.5 µg/dL [7-13; 8-10]; sCr, 70.4 µmol/L [61.6-79.2; 61.6-70.4]) (P = 0.35 and P = 0.41, respectively). Proteinuria in dogs with ADHAC-P was mainly of glomerular origin (SDS-AGE pattern: glomerular in 10/16 dogs; mixed glomerular/tubular in four dogs). In our study, SDMA was neither significantly different in dogs with ADHAC whether they were proteinuric or not, nor between ADHAC and healthy dogs. Urinary electrophoresis provides additional information to the UPC and further investigations are needed to determine whether it may help identify dogs with ADHAC-P requiring specific antiproteinuric treatment.

Asymmetric Dimethylarginine Is Associated with the Phenomenon of Coronary Slow Flow in Patients with Nonvalvular Atrial Fibrillation.

INTRODUCTION: Coronary slow flow phenomena (CSFP) are 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 levels of biological indicators. Our aim was to analyze the relationship between ADMA and CSFP in NVAF patients. METHODS: 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-selectin (p-sel), von Willebrand factor (vWF), D-dimer (D-Di), plasminogen activator inhibitor 1 (PAI-1), and nitric oxide (NO) were detected by ELISA in the different groups. RESULTS: 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-selectin, vWF, D-Di, and PAI-1) were significantly altered and correlated with ADMA levels. Multifactorial analysis showed that plasma ADMA (odd ratio [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. CONCLUSION: Our study demonstrated that CSFP in NVAF patients was associated with high levels of ADMA and left atrial internal diameter. Therefore, aggressive preoperative detection and evaluation of ADMA and left atrial internal diameter can help deal with the intraoperative presence of CSFP.

The diagnostic role of arginine-stimulated copeptin in the differential diagnosis of polyuria-polydipsia syndrome (PPS) in pediatric age.

PURPOSE: In recent years, copeptin stimulation through arginine administration has been evaluated as a new potential tool in the differential diagnosis of polyuria-polydipsia syndrome (PPS) in adults; to date very few data, all retrospective, exist in pediatric age. The aim of this prospective study is to evaluate the diagnostic performance of the arginine-stimulation test for copeptin in a cohort of pediatric patients affected by PPS. METHODS: All children (<18 years) referred to the Department of Pediatric Endocrinology of the Regina Margherita Children Hospital for polyuria-polydipsia in the period January 2021-June 2023 were enrolled. The Arginine-stimulation test for copeptin was performed in all patients presenting PPS after water deprivation test (WDT). Patients with polyuria-polydipsia were then classified as having primary polyuria (PP), complete and partial central diabetes insipidus (CDI), according to the standardized interpretation. Arginine-stimulation test for copeptin was also performed in a control cohort. RESULTS: A significant difference in arginine-stimulated copeptin values was observed at baseline (p = 0.005), at 60 min (p = 0.01), and at 90 min (p = 0.005) in 7 subjects presenting PP, 6 patients affected by CDI and 50 subjects of the control cohort. Plasma osmolality values remained stable at all measurements. The arginine-stimulated copeptin test demonstrated sensitivity and specificity of 100%, whereas the sensitivity of the WDT test was 83.3% and the specificity was 85.7%. CONCLUSION: Given the reliability and the minor adverse effects and costs, the copeptin level after arginine administration could replace the WDT in the diagnostic workup of these in pediatric age.

The relationship between reduced choroidal thickness due to high plasma asymmetrical dimethylarginine level and increased severity of diabetic retinopathy / Altos níveis de dimetil-arginina assimétrica no plasma podem aumentar a gravidade da retinopatia diabética através da redução da espessura da coroide

ABSTRACT Purpose: To evaluate the relationship between subfoveal choroidal thickness and plasma asymmetrical dimethylarginine level and the severity of diabetic retinopathy in patients with type 2 diabetes mellitus. Methods: A total of 68 cases, including 15 patients without diabetic retinopathy, 17 patients with nonproliferative diabetic retinopathy, 16 patients with type 2 diabetes mellitus and proliferative diabetic retinopathy, and 20 healthy patients (control group), were enrolled in this study. Subfoveal choroidal thickness was measured manually using the enhanced depth imaging optical coherence tomography scanning program, and plasma asymmetrical dimethylarginine level was measured using a commercial micro enzyme-linked immunosorbent assay kit. Results: The subfoveal choroidal thickness values and plasma asymmetrical dimethylarginine levels were significantly different between the four groups (p<0.001 and p<0.001). The subfoveal choroidal thickness values were significantly lower in the proliferative diabetic retinopathy group than in the other three groups (no diabetic retinopathy, nonproliferative diabetic retinopathy, and control groups; p<0.001, p=0.045, and p<0.001, respectively). The plasma asymmetrical dimethylarginine levels were significantly higher in the proliferative diabetic retinopathy group than in the other three groups (p<0.001, p<0.04, and p<0.001, respectively). In addition, a significant negative correlation was also found between plasma asymmetrical dimethylarginine level and subfoveal choroidal thickness (p<0.001, r=-0.479). Conclusion: Asymmetrical dimethylarginine is an important marker of endothelial dysfunction and endogenous endothelial nitric oxide synthase inhibitor. The severity of diabetic retinopathy was related to increased plasma asymmetrical dimethylarginine level and reduced subfoveal choroidal thickness in type 2 diabetic patients with diabetic retinopathy.

RESUMO Objetivo: Avaliar a relação da espessura subfoveal da coroide e dos níveis plasmáticos de dimetil-arginina assimétrica com a gravidade da retinopatia diabética em pacientes com diabetes mellitus tipo 2. Métodos: Foram incluídos 68 casos, compreendendo 15 pacientes sem retinopatia diabética, 17 pacientes com retinopatia diabética não proliferativa, 16 pacientes com retinopatia diabética proliferativa, e 20 casos saudáveis (grupo de controle). A espessura subfoveal da coroide foi medida manualmente, usando o programa de varredura com tomografia computadorizada óptica com imagem profunda aprimorada, e os níveis plasmáticos de dimetil-arginina assimétrica foram medidos usando um kit microELISA comercial. Resultados: Os valores da espessura subfoveal da coroide e os níveis plasmáticos de dimetil-arginina assimétrica foram significativamente diferentes nos quatro grupos (p<0,001 para ambos os parâmetros). Os valores da espessura subfoveal da coroide foram significativamente menores no grupo com retinopatia diabética proliferativa do que nos outros três grupos (sem retinopatia diabética, retinopatia diabética não proliferativa e grupo de controle, com p<0,001, p=0,045 e p<0,001, respectivamente). Já os níveis plasmáticos de dimetil-arginina assimétrica foram significativamente maiores no grupo com retinopatia diabética proliferativa do que nos outros três grupos (p<0,001, p=0,04 e p<0,001, respectivamente). Além disso, também foi encontrada uma correlação negativa significativa entre os níveis plasmáticos de dimetil-arginina assimétrica e a espessura subfoveal da coroide (p<0,001, r=-0,479). Conclusão: A dimetil-arginina assimétrica é um importante marcador de disfunção endotelial e um inibidor endógeno da óxido nítrico sintase. Foi encontrada uma relação da gravidade da retinopatia diabética e de níveis elevados de dimetil-arginina assimétrica no plasma com a redução da espessura subfoveal da coroide em pacientes diabéticos tipo 2 com retinopatia diabética.