Asymmetric and symmetric dimethylarginine gingival crevicular fluid levels in periodontitis.

OBJECTIVE: This study aimed to evaluate the level of ADMA (asymmetric dimethylarginine), SDMA (symmetric dimethylarginine), and IL-1ß (Interleukin-1ß) in gingival crevicular fluid (GCF) from periodontitis patients and control subjects. BACKGROUND: ADMA and SDMA are potentially hazardous non-proteinogenic amino acids that limit nitric oxide (NO) synthesis and have many functions in various human disorders. ADMA causes a structural change in nitric oxide synthase, while SDMA blocks arginine cell uptake. Increased plasma ADMA has been widely recognized as a "trigger" initiating impaired NO bioavailability and vascular dysfunction, which ultimately leads to oxidative stress. METHODS: Twenty-five patients with periodontitis (P) (Stage III, Grade C, n = 25) and 20 control (C) subjects were included in the study. The IL-1ß level of GCF was measured by enzyme immunoassay (ELISA) and ADMA and SDMA by liquid chromatography-mass spectrometry (LC-MS/MS). RESULTS: Periodontitis patients had higher clinical parameters than controls (p < .001). Levels of IL-1ß, ADMA and SDMA GCF were statistically significantly higher in group P than in group C (respectively; p = .003, p < .0001, p < .0001). There was no difference in the ADMA/SDMA ratio (p = .312) between the groups. There were significant positive correlations between clinical periodontal parameters and IL-1ß, ADMA, and SDMA levels (p < .05). ADMA and SDMA levels were significantly correlated with IL-1ß (p < .05). CONCLUSIONS: These findings suggest that ADMA and SDMA may be involved in the pathogenesis of the periodontal disease.

Simultaneous determination of N(G)-monomethyl-L-arginine, N(G),N(G)-dimethyl-L-arginine, N(G),N(G')-dimethyl-L-arginine, and L-arginine using monolithic silica disk-packed spin columns and a monolithic silica column.

We have developed and validated a high-performance liquid chromatography method that uses monolithic silica disk-packed spin columns and a monolithic silica column for the simultaneous determination of N(G)-monomethyl-L-arginine, N(G),N(G)-dimethyl-L-arginine, and N(G),N(G')-dimethyl-L-arginine in human plasma. For solid-phase extraction, our method employs a centrifugal spin column packed with monolithic silica bonded to propyl benzenesulfonic acid as a cation exchanger. After pretreatment, the methylated arginines are converted to fluorescent derivatives with 4-fluoro-7-nitro-2,1,3-benzoxadiazole, and then the derivatives are separated on a monolithic silica column. L-arginine concentration was also determined in diluted samples. Standard calibration curves revealed that the assay was linear in the concentration range 0.2-1.0 µM for methylated arginines and 40-200 µM for L-arginine. Linear regression of the calibration curve yielded equations with correlation coefficients of 0.999 (r(2)). The sensitivity was satisfactory, with a limit of detection ranging from 3.75 to 9.0 fmol for all four compounds. The RSDs were 4.3-4.8% (intraday) and 3.0-6.8% (interday). When this method was applied to samples from six healthy donors, the detected concentrations of N(G)-monomethyl-L-arginine, N(G),N(G)-dimethyl-L-arginine, N(G),N(G')-dimethyl-L-arginine and L-arginine were 0.05 ± 0.01, 0.41 ± 0.07, 0.59 ± 0.11, and 83.8 ± 30.43 µM (n = 6), respectively.

Maladaptive Pulmonary Vascular Responses to Chronic Sustained and Chronic Intermittent Hypoxia in Rat.

Chronic sustained hypoxia (CSH), as found in individuals living at a high altitude or in patients suffering respiratory disorders, initiates physiological adaptations such as carotid body stimulation to maintain oxygen levels, but has deleterious effects such as pulmonary hypertension (PH). Obstructive sleep apnea (OSA), a respiratory disorder of increasing prevalence, is characterized by a situation of chronic intermittent hypoxia (CIH). OSA is associated with the development of systemic hypertension and cardiovascular pathologies, due to carotid body and sympathetic overactivation. There is growing evidence that CIH can also compromise the pulmonary circulation, causing pulmonary hypertension in OSA patients and animal models. The aim of this work was to compare hemodynamics, vascular contractility, and L-arginine-NO metabolism in two models of PH in rats, associated with CSH and CIH exposure. We demonstrate that whereas CSH and CIH cause several common effects such as an increased hematocrit, weight loss, and an increase in pulmonary artery pressure (PAP), compared to CIH, CSH seems to have more of an effect on the pulmonary circulation, whereas the effects of CIH are apparently more targeted on the systemic circulation. The results suggest that the endothelial dysfunction evident in pulmonary arteries with both hypoxia protocols are not due to an increase in methylated arginines in these arteries, although an increase in plasma SDMA could contribute to the apparent loss of basal NO-dependent vasodilation and, therefore, the increase in PAP that results from CIH.

Assessment of serum galectin-3, methylated arginine and Hs-CRP levels in type 2 diabetes and prediabetes.

PURPOSE: Galectin-3 is associated with the process of inflammation and fibrosis. The aim of this study was both to evaluate of galectin-3, methylated arginines and hs-CRP in subjects with type 2 diabetes and prediabetes and to investigate a relation between serum galectin-3, methylated arginines and hs-CRP levels. METHODS: In this study, all subjects were defined as the control group, type 2 diabetes (n = 84) by fasting plasma glucose and prediabetes (n = 34) by 75-g oral glucose tolerance test. Also, participants with type 2 diabetes were divided into as group I (HbA1c ≤7%, n = 40) and group II (HbA1c ≥7%, n = 44). The analysis of serum methylated arginines levels was analyzed by tandem mass spectrometry. Galectin-3 levels were determined via chemiluminescent microparticle immunoassay (CMIA). RESULTS: Serum galectin-3, ADMA, L-NMMA and SDMA levels were significantly lower in the control group (13.3 ±â€¯3.42; 0.630 (0.13-1.36); 0.176 (0.02-0.53); 0.115 (0.04-0.26), respectively) compared to diabetic subjects (15.71 ±â€¯4.22; 0.825 (0.23-2.80); 0.366 (0.08-1.41); 0.1645 (0.06-0.47), p = 0.002, p = 0.01, p = 0.001 and p = 0.006, respectively). Galectin-3 was positively correlated with hs-CRP (r = 0.295 p = 0.001), L-NMMA (r = 0.181 p = 0.022), HbA1c (r = 0.247 p = 0.002), neopterin (r = 0.160 p = 0.045) and FPG (r = 0.207 p = 0.001) respectively. Also, there was positively correlated ADMA with FPG (r = 0.192 p = 0.016) and eAG (r = 0.235 p = 0.003). CONCLUSIONS: Thus, galectin-3 might be a useful prognostic marker in the population with prediabetes and diabetes. Moreover, it can be a marker showing the condition of developing complications in diabetic patients.

Plasma Symmetric Dimethylarginine Concentration in Dogs with Acute Kidney Injury and Chronic Kidney Disease.

BACKGROUND: Symmetric dimethylarginine (SDMA) is considered a biomarker for early detection of renal dysfunction in human patients with acute kidney injury (AKI). At present, no studies exist analyzing the relevance of SDMA in dogs with AKI. HYPOTHESIS/OBJECTIVES: SDMA would correctly identify dogs with renal disease but would not be able to differentiate between AKI and CKD. ANIMALS: Eighteen healthy control dogs, 48 dogs with AKI, and 29 dogs with CKD. METHODS: Prospective study. Dogs with kidney disease were categorized as having AKI or CKD according to the history, clinical signs, laboratory findings, and results of diagnostic imaging. Plasma SDMA concentration was measured by IDEXX Laboratories. SDMA/creatinine ratio was calculated in dogs with AKI or CKD. RESULTS: Median SDMA concentrations were 8.5 µg/dL (6-12 µg/dL), 39.5 µg/dL (8->100 µg/dL), and 35 µg/dL (12->100 µg/dL), in healthy, AKI, and CKD, respectively. SDMA concentrations were significantly higher in dogs with AKI (P < .0001) or CKD (P < .0001) in comparison with healthy dogs. Median SDMA/creatinine ratio in dogs with AKI and CKD was 6.5 (1.7-20.9) and 10 (2.4-33.9) (P = .0004), respectively. Although there was overlap of the SDMA/creatinine ratio in dogs with AKI or CKD, it was significantly higher in dogs with CKD compared to dogs with AKI (P = .0004). CONCLUSIONS AND CLINICAL IMPORTANCE: In this population, SDMA was suitable for identifying dogs affected by AKI or CKD, but could not differentiate between them.