Associations between endogenous dimethylarginines and renal function in healthy children and adolescents

The structural isomer of asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), is eliminated almost entirely by urinary excretion and considered a sensitive index of glomerular filtration rate (GFR). However, reports on this relationship in healthy subjects younger than 18 years of age are rare. Therefore, our aim was to investigate relations between endogenous dimethylarginines and renal function indices in healthy children and adolescents. We studied 40 subjects aged 3–18 years free of coexistent diseases or subclinical carotid atherosclerosis. A serum creatinine-derived estimated GFR (eGFR) was calculated by the revised bedside Schwartz equation. L-arginine, ADMA and SDMA were measured by liquid chromatography-tandem mass spectrometry. Mean eGFR was 122 ± 22 (SD) mL/min per 1.73 m2. Creatinine and eGFR exhibited closer correlations with the SDMA/ADMA ratio (r = 0.64, p < 0.0001; r = −0.63, p < 0.0001, respectively) than with SDMA (r = 0.31, p = 0.05; r = −0.35, p = 0.03). Neither creatinine nor eGFR correlated with ADMA or L-arginine. Adjustment for age or height only slightly attenuated the associations between the SDMA/ADMA ratio and eGFR or creatinine. Our findings suggest the superiority of the SDMA/ADMA ratio over SDMA as a renal function index in healthy children. Thus, further studies are warranted to verify our preliminary results in a larger group of subjects below 18 years of age

A Model for Neutrino Warm Dark Matter and Neutrino Oscillations

The muon- and tau-neutrinos with the mass in the keV range, which are allowed in a low reheating temperature cosmology, can compose the warm dark matter of the universe. A model of four light neutrinos including the keV scale $\nu_\mu$ and $\nu_\tau$ is studied, which combines the seesaw mechanism and the Abelian flavor symmetry. The atmospheric neutrino anomaly is due to the $\nu_\mu-\nu_\tau$ oscillation. The solar neutrino problem is answered by the oscillation into the light sterile neutrino, where the SMA, LMA, and LOW-QVO solutions can be accommodated in our scenario.Comment: 11 pages, Final version to appear in PLB, References adde

Long-term glycine propionyl-l-carnitine supplemention and paradoxical effects on repeated anaerobic sprint performance

<p>Abstract</p> <p>Background</p> <p>It has been demonstrated that acute GPLC supplementation produces enhanced anaerobic work capacity with reduced lactate production in resistance trained males. However, it is not known what effects chronic GPLC supplementation has on anaerobic performances or lactate clearance.</p> <p>Purpose</p> <p>The purpose of this study was to examine the long-term effects of different dosages of GPLC supplementation on repeated high intensity stationary cycle sprint performance.</p> <p>Methods</p> <p>Forty-five resistance trained men participated in a double-blind, controlled research study. All subjects completed two testing sessions, seven days apart, 90 minutes following oral ingestion of either 4.5 grams GPLC or 4.5 grams cellulose (PL), in randomized order. The exercise testing protocol consisted of five 10-second Wingate cycle sprints separated by 1-minute active recovery periods. Following completion of the second test session, the 45 subjects were randomly assigned to receive 1.5 g, 3.0 g, or 4.5 g GPLC per day for a 28 day period. Subjects completed a third test session following the four weeks of GPLC supplementation using the same testing protocol. Values of peak power (PP), mean power (MP) and percent decrement of power (DEC) were determined per bout and standardized relative to body mass. Heart rate (HR) and blood lactate (LAC) were measured prior to, during and following the five sprint bouts.</p> <p>Results</p> <p>There were no significant effects of condition or significant interaction effects detected for PP and MP. However, results indicated that sprint bouts three, four and five produced 2 - 5% lower values of PP and 3 - 7% lower values of MP with GPLC at 3.0 or 4.5 g per day as compared to baseline values. Conversely, 1.5 g GPLC produced 3 - 6% higher values of PP and 2 -5% higher values of MP compared with PL baseline values. Values of DEC were significantly greater (15-20%) greater across the five sprint bouts with 3.0 g or 4.5 g GPLC, but the 1.5 g GPLC supplementation produced DEC values -5%, -3%, +4%, +5%, and +2% different from the baseline PL values. The 1.5 g group displayed a statistically significant 24% reduction in net lactate accumulation per unit power output (p < 0.05).</p> <p>Conclusions</p> <p>The effects of GPLC supplementation on anaerobic work capacity and lactate accumulation appear to be dosage dependent. Four weeks of GPLC supplementation at 3.0 and 4.5 g/day resulted in reduced mean values of power output with greater rates of DEC compared with baseline while 1.5 g/day produced higher mean values of MP and PP with modest increases of DEC. Supplementation of 1.5 g/day also produced a significantly lower rate of lactate accumulation per unit power output compared with 3.0 and 4.5 g/day. In conclusion, GPLC appears to be a useful dietary supplement to enhance anaerobic work capacity and potentially sport performance, but apparently the dosage must be determined specific to the intensity and duration of exercise.</p

Asymmetric Dimethylarginine, Endothelial Nitric Oxide Bioavailability and Mortality in Sepsis

Background: Plasma concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxidesynthase, are raised in patients with chronic vascular disease, causing increased cardiovascular risk and endothelialdysfunction, but the role of ADMA in acute inflammatory states is less well defined.Methods and Results: In a prospective longitudinal study in 67 patients with acute sepsis and 31 controls, digitalmicrovascular reactivity was measured by peripheral arterial tonometry and blood was collected at baseline and 2&ndash;4 dayslater. Plasma ADMA and L-arginine concentrations were determined by high performance liquid chromatography. Baselineplasma L-arginine: ADMA ratio was significantly lower in sepsis patients (median [IQR] 63 [45&ndash;103]) than in hospital controls(143 [123&ndash;166], p,0.0001) and correlated with microvascular reactivity (r = 0.34, R2 = 0.12, p = 0.02). Baseline plasma ADMAwas independently associated with 28-day mortality (Odds ratio [95% CI] for death in those in the highest quartile($0.66 mmol/L) = 20.8 [2.2&ndash;195.0], p = 0.008), and was independently correlated with severity of organ failure. Increase inADMA over time correlated with increase in organ failure and decrease in microvascular reactivity.Conclusions: Impaired endothelial and microvascular function due to decreased endothelial NO bioavailability is a potentialmechanism linking increased plasma ADMA with organ failure and death in sepsis

Glycine propionyl-L-carnitine increases plasma nitrate/nitrite in resistance trained men

We have recently demonstrated that oral intake of glycine propionyl-L-carnitine (GPLC) increases plasma nitrate/nitrite (NOx), a surrogate measure of nitric oxide production. However, these findings were observed at rest, and in previously sedentary subjects

Citrulline a More Suitable Substrate than Arginine to Restore NO Production and the Microcirculation during Endotoxemia

BACKGROUND: Impaired microcirculation during endotoxemia correlates with a disturbed arginine-nitric oxide (NO) metabolism and is associated with deteriorating organ function. Improving the organ perfusion in endotoxemia, as often seen in patients with severe infection or systemic inflammatory response syndrome (SIRS) is, therefore, an important therapeutic target. We hypothesized that supplementation of the arginine precursor citrulline rather than arginine would specifically increase eNOS-induced intracellular NO production and thereby improve the microcirculation during endotoxemia. METHODOLOGY/PRINCIPAL FINDINGS: To study the effects of L-Citrulline and L-Arginine supplementation on jejunal microcirculation, intracellular arginine availability and NO production in a non-lethal prolonged endotoxemia model in mice. C57/Bl6 mice received an 18 hrs intravenous infusion of endotoxin (LPS, 0.4 µg • g bodyweight(-1) • h(-1)), combined with either L-Citrulline (6.25 mg • h-1), L-Arginine (6.25 mg • h(-1)), or L-Alanine (isonitrogenous control; 12.5 mg • h(-1)) during the last 6 hrs. The control group received an 18 hrs sterile saline infusion combined with L-Alanine or L-Citrulline during the last 6 hrs. The microcirculation was evaluated at the end of the infusion period using sidestream dark-field imaging of jejunal villi. Plasma and jejunal tissue amino-acid concentrations were measured by HPLC, NO tissue concentrations by electron-spin resonance spectroscopy and NOS protein concentrations using Western blot. CONCLUSION/SIGNIFICANCE: L-Citrulline supplementation during endotoxemia positively influenced the intestinal microvascular perfusion compared to L-Arginine-supplemented and control endotoxemic mice. L-Citrulline supplementation increased plasma and tissue concentrations of arginine and citrulline, and restored intracellular NO production in the intestine. L-Arginine supplementation did not increase the intracellular arginine availability. Jejunal tissues in the L-Citrulline-supplemented group showed, compared to the endotoxemic and L-Arginine-supplemented endotoxemic group, an increase in degree of phosphorylation of eNOS (Ser 1177) and a decrease in iNOS protein level. In conclusion, L-Citrulline supplementation during endotoxemia and not L-Arginine reduced intestinal microcirculatory dysfunction and increased intracellular NO production, likely via increased intracellular citrulline and arginine availability