Endogenous Nitric Oxide Synthesis Inhibitor Asymmetrical Dimethyl-L-Arginine (ADMA) and Neoplasms in Children

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5469-5469
Author(s):  
Adrian Doroszko ◽  
Ewa Niedzielska ◽  
Dorota Wojcik ◽  
Elzbieta Wojcik ◽  
Andrzej Szuba ◽  
...  
Keyword(s):  
Plasma Level ◽  
Solid Tumor ◽  
Clinical Stage ◽  
Plasma Concentrations ◽  
Control Group ◽  
Nitric Oxide Synthesis ◽  
Elevated Plasma ◽  
Synthesis Inhibitor ◽  
Oncological Treatment ◽  
Endogenous Nitric Oxide

Abstract Background: Neoplasms in children are uncommon diseases however they have broad impact on the society. Despite novel therapeutic strategies for children suffering from leukemia or solid tumor, the mortality rate of the disease is still high. The endogenous nitric oxide synthesis inhibitor asymmetrical dimethyl-L-arginine (ADMA) is considered to be a strong cardirovascular risk factor and may lead to new therapeutic strategies. Our previous findings indicate that elevated plasma level of ADMA is correlated with worse prognosis in adult patients with NHL. There are no data available pointing at metabolites of NO-pathway nor clinical evidence as prognostic factor of oncological treatment in children. Aim: To investigate the relation between elevated plasma level of NO-pathway metabolites and well established markers of clinical stage of the disease. Material and method: 12 children with acute leukemias (ALL, AML), 13 with solid tumor (PNET, osteosarcoma, Wilms’ tumor, RMS) during hemato-oncological treatment were recruited to a pilot study and N=15 healthy children to a control group. Plasma concentrations of ADMA, SDMA, L-Arg was determined. Relationship to clinical stage of the disease, biochemical and blood markers was tested. Results Table 1: Differences in mean plasma concentrations of arginine, ADMA and SDMA in pts with leukemia vs pts with solid tumor vs control group Control:N=15 Mean ±SD Median ±SEM Leukemia;N=12 Mean±SD Median ±SEM Solid tumour; N=13 Mean±SD Median ±SEM P L-Arg 68,58±24,29 60,19±6,27 31,28±8,63 30,82±2,49 49,59±10,81 49,18±3,00 0,0000 ADMA 0,62±0,10 0,61±0,02 1,17±1,10 0,53±0,32 0,98±1,10 0,46±0,31 NS SDMA 0,44±0,18 0,39±0,04 1,18±1,10 0,80±0,32 1,56±1,02 1,09±0,28 0,0024 ARG/ADMA 112,8±46,28 107,4±11,94 67,40±54,31 69,48±15,68 228,82±451,44 117,35±125,21 NS Table 2:Significant correlations in group of pts with solid tumor and in patients with leukemia LEUKEMIA; N=12 R p ADMA & Ca 0,78 0,008 SDMA & Ca 0,75 0,011 SDMA & CRP −0,78 0,021 Arg/ADMA & K −0,72 0,019 Arg/ADMA & Ca −0,64 0,043 Arg& MONOCYTE 0,65 0,043 ADMA & TOT.BILIRUB. −0,92 0,000 ADMA & TOT.PROTEIN 0,75 0,032 SDMA & EOSINOPHILE 0,73 0,025 SDMA & TOT.BILIRUB −0,82 0,007 Arg/ADMA & TOT.BILIRUB. 0,81 0,009 SOLID TUMOR; N=15 R p Arg &RBC 0,70 0,016 Arg & Hb 0,64 0,035 Arg & LYMPHOCYTE 0,81 0,003 Arg & EOSINOPHILE 0,76 0,011 ADMA &MONOCYTE −0,78 0,008 ADMA & TOT.PROTEIN 0,62 0,040 ADMA & Hb 0,64 0,035 Arg/ADMA &MONOCYTE 0,82 0,004 Arg/ADMA & BASOPHILE 0,65 0,043 Conclusions:A lower plasma level of L-Arg was found both in pts with leukemia and solid tumors. Higher plasma concentration of SDMA was found in patients with leukemia and solid tumor compared to the control group. Further studies are necessary to clarify the significance of these findings.

Leukemia, Solid Tumors and Methylarginines: Is There Any Relation?

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5471-5471
Author(s):  
Adrian Doroszko ◽  
Ewa Niedzielska ◽  
Dorota Wojcik ◽  
Andrzej Szuba ◽  
Ryszard Andrzejak
Keyword(s):  
Nitric Oxide ◽  
Plasma Level ◽  
Solid Tumors ◽  
Solid Tumor ◽  
Wilms Tumor ◽  
Plasma Concentrations ◽  
Synthesis Inhibitor ◽  
Significant Treatment ◽  
Acute Leukemias ◽  
Cardiovascular Morbidity And Mortality

Abstract Background: Despite improvements achieving complete remission and progress in supportive care of children with acute leukemias or solid tumors during the last decade, there are no optimal prognostic markers in stratification of risk of adverse events leading to poor outcome. The endogenous nitric oxide synthesis inhibitor asymmetrical dimethyl-L-arginine (ADMA) is associated with atherosclerosis and represents an independent marker for cardiovascular morbidity and mortality. Aim: To investigate the clinical significance of methylarginines in leukemia and solid tumors in children. Material and method: Concentration of metabolites of nitric-oxide pathway in children during therapy of acute leukemia (ALL) – N 12 and solid tumors N 15 (osteosarcoma, RMS, PNET, Wilms’ tumor) was determined. Correlations of biochemical markers, blood count parameters and plasma level of methylarginines were investigated. In addition, the influence of cytostatics on NO-pathway metabolites was analyzed. Results: Table 1: Differences in mean plasma concentration of arginine, ADMA and SDMA in pts with leukemia vs pts with solid tumor Leukemia N=12 Mean ±SD Median±SEM Solid tumor N=15 Mean ±SD Median±SEM p Arg 31,28±8,63 30,82±2,49 49,59±10,81 49,18±3,00 0,0003 ADMA 1,17±1,10 0,53±0,32 0,98±1,10 0,46±0,31 NS SDMA 1,18±1,10 0,80±0,32 1,56±1,02 1,09±0,28 NS Arg/ADMA 67,40±54,31 69,48±15,68 228,82±451,44 117,35±125,21 NS Table.2. Differences in mean plasma concentrations of arginine, ADMA and SDMA depending on gender, treatment, etc. N=27 Arginine ADMA SDMA Arg/ADMA Sex 1. Mail; 2. Femail 1. 0.NS NS NS NS HSCT (1-yes; 0-no) 1. 0.NS NS NS NS Remission (1-yes; 0-no) 1. 0.NS NS NS NS Currently infection (1-yes; 0-no) 1. 0.NS NS NS NS Glucocoricoids (1-yes; 0-no) 1. 31,9±9,30. 51,0±11,2 p=0,0011 NS NS NS Cytostatic – any (1-yes; 0-no) 1. 0. NS NS NS NS Doxorubicine (1-yes; 0-no) 1. 0. NS NS NS NS Vincristine (1-yes; 0-no) 1. 0. NS NS NS NS Cytarabine (1-yes; 0-no) 1. 32,0±10,50. 45,6±10,8 p=0,022 NS NS NS Methotrexate (1-yes; 0-no) 1.0 NS NS NS NS Thioguanine/6-merkaptopurine(1-yes; 0-no) 1. 0. NS NS NS NS Cyclophosphamide/Iphosphamide(1-yes; 0-no) 1. 0. NS NS NS NS Conclusions: Plasma level of L-Arg was significantly higher in patients with solid tumor The L-Arg/ADMA ratio was not significantly higher in patients with solid tumors and lower plasma level of ADMA was found. Treatment with glucocorticoids and cytarabine was associated with significantly lower level of L-Arg. No significant treatment dependent difference was found in level of nitric oxide metabolic pathway.

Elevated Plasma Aluminum Levels in Normal Infants Receiving Antacids Containing Aluminum

PEDIATRICS ◽  
1991 ◽  
Vol 87 (2) ◽  
pp. 148-151
Author(s):  
V. Marc Tsou ◽  
Rose M. Young ◽  
Michael H. Hart ◽  
Jon A. Vanderhoof
Keyword(s):  
Renal Function ◽  
Plasma Level ◽  
Normal Renal Function ◽  
Aluminum Toxicity ◽  
Control Group ◽  
Elevated Plasma ◽  
Careful Monitoring ◽  
Aluminum Level ◽  
Aluminum Accumulation ◽  
High Doses

Aluminum toxicity is a documented cause of encephalopathy, anemia, and osteomalacia. Excretion is primarily renal; therefore, patients with renal insufficiency are at risk for aluminum accumulation and toxicity. This has been demonstrated in uremic children treated with aluminum-containing antacids. The purpose of this study was to determine whether plasma aluminum levels were elevated in infants with normal renal function during prolonged aluminum-containing antacid use. Ten study infants (mean age = 5.8 months), who had been receiving antacids for at least 1 week, were compared with 16 control infants (mean age = 9.8 months) not receiving antacids. The study patients consumed 123 ± 16 mg/kg per day (mean ± SEM) of elemental aluminum for an average of 4.7 weeks. Their plasma aluminum level (37.2 ± 7.13 µg/L) was significantly greater than that of the control group (4.13 ± 0.66 µg/L) (P < .005). It is concluded that plasma aluminum levels may become elevated in infants with normal renal function who are consuming high doses of aluminum-containing antacids. The safety of antacids containing aluminum should not be assumed and they should be used judiciously in infants, with careful monitoring of the aluminum dose and plasma level.

THE PLASMA CONCENTRATIONS OF FREE AND PROTEIN-BOUND CORTISOL IN HYPOPROTEINAEMIA

1966 ◽  
Vol 34 (2) ◽  
pp. 265-270 ◽  
Author(s):  
P. J. LEONARD ◽  
P. G. D'ARBELA
Keyword(s):  
Plasma Level ◽  
Cortisol Level ◽  
Plasma Concentrations ◽  
Biochemical Changes ◽  
Striking Similarity ◽  
Control Group ◽  
Absolute Level ◽  
Total Cortisol ◽  
Control Subjects ◽  
Free Cortisol

SUMMARY The plasma level and percentage of bound cortisol were measured in sixteen African subjects with hypoproteinaemia of varying aetiologies. When compared with a control group it was found that the percentage of the steroid bound was significantly reduced but that the total cortisol level did not differ from that found in the control subjects. This resulted in a significant increase in the absolute level of free cortisol in the hypoproteinaemic subjects. Attention is drawn to the striking similarity between many of the physical and biochemical changes seen in kwashiorkor and those found in Cushing's syndrome.

scholarly journals Endogenous Nitric Oxide Synthesis Inhibitor Asymmetric Dimethyl l -Arginine Accelerates Endothelial Cell Senescence

2004 ◽  
Vol 24 (10) ◽  
pp. 1816-1822 ◽  
Author(s):  
Fortunato Scalera ◽  
Jürgen Borlak ◽  
Bibiana Beckmann ◽  
Jens Martens-Lobenhoffer ◽  
Thomas Thum ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cell ◽  
Cell Senescence ◽  
Nitric Oxide Synthesis ◽  
Synthesis Inhibitor ◽  
Endogenous Nitric Oxide

scholarly journals Serum N-Acetylneuraminic Acid Is Associated with Atrial Fibrillation and Left Atrial Enlargement

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Wei Hu ◽  
Jing Xie ◽  
Tongjian Zhu ◽  
Guannan Meng ◽  
Meng Wang ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Plasma Level ◽  
Odds Ratio ◽  
Left Atrial ◽  
Plasma Concentrations ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Left Atrial Enlargement ◽  
Acetylneuraminic Acid ◽  
Atrial Enlargement

Purpose. Recent studies have indicated that N-acetylneuraminic acid (Neu5Ac) plays a key role in severe coronary artery diseases, involving RhoA signaling pathway activation, which is critically involved in cardiac fibrosis. There is convincing evidence from many studies that left atrium fibrosis is involved in the pathophysiology of AF. Therefore, we speculated that Neu5Ac may be associated with atrial fibrillation (AF) and involved in the development of AF. This study aims to investigate the clinical relationship between Neu5Ac and AF and left atrial enlargement. Methods. Forty-five patients with AF (AF group) and forty-five patients with non-AF (control group) matched for age, sex, and hospitalization date were recruited for our study. Plasma concentrations of Neu5Ac from peripheral venous blood were analyzed using enzyme-linked immunosorbent assay (ELISA). The baseline characteristics, plasma level of Neu5Ac, and echocardiographic characteristics were evaluated. Results. The plasma level of Neu5Ac was significantly higher in the AF group than in the control group (107.66 ± 47.50 vs 77.87 ± 39.09  ng/ml; P<0.05); the left atrial diameters were positively correlated with the plasma Neu5Ac level (R = 0.255; P<0.05). The plasma Neu5Ac level (R = 0.368; P<0.05) and the left atrial diameters (R = 0.402; P<0.05) were positively correlated with AF history times. Neu5Ac (odds ratio 1.018, 95% CI 1.003–1.032; P<0.05) and the left atrial diameter (odds ratio 1.142, 95% CI 1.020–1.280; P<0.05) were independent risk factors for AF in multivariate regression analysis. Conclusions. Serum Neu5Ac is associated with atrial fibrillation, and the mechanism may involve left atrial enlargement.

Elevated plasma concentrations of beta-cell tropin (ACTH22-39) in diet-treated type II diabetic patients

Diabetes ◽  
1992 ◽  
Vol 41 (9) ◽  
pp. 1160-1164 ◽  
Author(s):  
J. C. Levy ◽  
J. L. Morton ◽  
M. Davenport ◽  
A. Beloff-Chain ◽  
R. C. Turner
Keyword(s):  
Beta Cell ◽  
Plasma Concentrations ◽  
Diabetic Patients ◽  
Type Ii ◽  
Elevated Plasma

Evaluation of plasma free amino acid and carnitine levels in patients with cesarean scar pregnancy

2020 ◽  
Vol 23 ◽  
Author(s):  
Omer Tammo ◽  
Hacer Uyanikoglu ◽  
İsmail Koyuncu
Keyword(s):  
Amino Acid ◽  
Pregnant Women ◽  
Free Amino Acid ◽  
Free Amino ◽  
Plasma Concentrations ◽  
Myometrial Invasion ◽  
Controlled Study ◽  
Control Group ◽  
Cesarean Scar Pregnancy ◽  
Cesarean Scar

Aim and Objective: This study aimed to explore the plasma free amino acid (FAA) and carnitine levels in pregnant women with cesarean scar pregnancy (CSP), and to compare them with those of healthy pregnant women. Materials and Methods: This prospective and randomized controlled study was conducted in patients admitted to Harran University Medical Faculty Hospital Obstetrics Clinic between January 2018 and January 2019. A total of 60 patients were included in the study, and the patients were divided into two groups: CSP group (n = 30) and healthy pregnant group as the control group (n = 30). The blood samples were taken from the participants between 7 - 12 weeks of gestation. Twentyseven carnitines and their esters and 14 FAAs were analysed by liquid chromatography – mass spectrometry (LC-MS/MS). Results: The mean plasma concentrations of some carnitines, including C2, C5, C5-OH, C5-DC, C6, C8-1, C12, C14, C14- 1, C14-2, C16, C16-1, C18, and C18-1 were significantly higher in CSP group than in the control group. However, other carnitines, including C0, C3, C4, C4-DC, C5-1, C6-DC, C8, C8-DC, C10, C10-1, C18-1-OH, and C18-2 were similar in both groups. The plasma levels of some FAAs, including Methyl Glutaryl, Leu, Met, Phe, Arg, Orn, and Glu values were significantly higher in CSP group than in the control group. However, there was no statistically significance in other FAA levels, including Val, Asa, Tyr, Asp, Ala, Cit, and Gly between the two groups. Additionally, Pearson’s correlation analysis showed that there were significantly positive correlations between many FAA and carnitine values. Conclusion: Since several plasma carnitine and FAA levels were higher in CSP group than in the control group, we think that scar pregnancy increases metabolic need for myometrial invasion. Also, we think that these results may be useful in clinical practice for CSP diagnosis.

Clinical Impact of Co-medication of Levetiracetam and Clobazam with Proton Pump Inhibitors: A Drug Interaction Study

2020 ◽  
Vol 21 (2) ◽  
pp. 126-131
Author(s):  
Bhuvanachandra Pasupuleti ◽  
Vamshikrishna Gone ◽  
Ravali Baddam ◽  
Raj Kumar Venisetty ◽  
Om Prakash Prasad
Keyword(s):  
Plasma Concentration ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Plasma Concentrations ◽  
Control Group ◽  
Drug Concentrations ◽  
Significant Difference ◽  
Post Hoc ◽  
Hydrolysis Of ◽  
Cytochrome P 450

Background: Clobazam (CLBZ) metabolized primarily by Cytochrome P-450 isoenzyme CYP3A4 than with CYP2C19, Whereas Levetiracetam (LEV) is metabolized by hydrolysis of the acetamide group. Few CYP enzymes are inhibited by Proton Pump Inhibitors (PPIs) Pantoprazole, Esomeprazole, and Rabeprazole in different extents that could affect drug concentrations in blood. The aim of the present study was to evaluate the effect of these PPIs on the plasma concentrations of LEV and CLBZ. Methods: Blood samples from 542 patients were included out of which 343 were male and 199 were female patients and were categorized as control and test. Plasma samples analyzed using an HPLC-UV method. Plasma concentrations were measured and compared to those treated and those not treated with PPIs. One way ANOVA and games Howell post hoc test used by SPSS 20 software. Results: CLBZ concentrations were significantly 10 folds higher in patients treated with Pantoprazole (P=0.000) and 07 folds higher in patients treated with Esmoprazole and Rabeprazole (P=0.00). Whereas plasma concentration of LEV control group has no statistical and significant difference when compared to pantoprazole (P=0.546) and with rabeprazole and esomeprazole was P=0.999. Conclusion: The effect of comedication with PPIs on the plasma concentration of clobazam is more pronounced for pantoprazole to a greater extent when compared to esomeprazole and rabeprazole. When pantoprazole is used in combination with clobazam, dose reduction of clobazam should be considered, or significance of PPIs is seen to avoid adverse effects.

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