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1.
Metabolites ; 12(11)2022 Nov 12.
Article in English | MEDLINE | ID: mdl-36422244

ABSTRACT

Acquired vitamin B12 (vB12) deficiency (vB12D) of newborns is relatively frequent as compared with the incidence of inherited diseases included in newborn screening (NBS) of different countries across the globe. Infants may present signs of vB12D before 6 months of age with anemia and/or neurologic symptoms when not diagnosed in asymptomatic state. The possibility of identifying vitamin deficient mothers after their pregnancy during the breastfeeding period could be an additional benefit of the newborn screening. Vitamin supplementation is widely available and easy to administer. However, in many laboratories, vB12D is not included in the national screening program. Optimized screening requires either second-tier testing or analysis of new urine and blood samples combined with multiple clinical and laboratory follow ups. Our scope was to review the physiologic fate of vB12 and the pathobiochemical consequences of vB12D in the human body. Particular emphasis was put on the latest approaches for diagnosis and treatment of vB12D in NBS.

2.
Article in English | MEDLINE | ID: mdl-34225243

ABSTRACT

Simultaneous determination of kynurenines, neurotransmitters, pterins and steroids linked to various neurological and metabolic diseases have important diagnostic significance for related pathology and drug monitoring. An improved, sensitive and selective ultra-high performance liquid chromatography coupled to electrospray ionization triple quadrupole mass spectrometric (UHPLC-MS/MS) method, based on our earlier publication, has been proposed for the quantitative measurement of 42 metabolites in human urine. The assay covers a larger number of analytes, uses an advanced, Waters Atlantis T3 chromatographic column and similarly meets the guideline of European Medicines Agency (EMA) on bioanalytical method validation. Analytical performance met all the EMA requirements and the assay covered the relevant clinical concentrations. Linear correlation coefficients were all > 0.998. Intra-day and inter-day accuracy and precision were 87-118%, 81-120% and 2-20%, respectively including the lower limit of quantification (LLOQ). The assay is expected to facilitate the diagnosis and allows drug level monitoring from urine.


Subject(s)
Chromatography, Liquid/methods , Neurotransmitter Agents/urine , Pterins/urine , Tandem Mass Spectrometry/methods , Adult , Biomarkers/urine , Humans , Kynurenine/urine , Linear Models , Middle Aged , Reproducibility of Results , Sensitivity and Specificity
3.
PLoS One ; 16(5): e0252091, 2021.
Article in English | MEDLINE | ID: mdl-34015037

ABSTRACT

In newborn screening, samples suspected for congenital adrenal hyperplasia (CAH), a potentially lethal inborn error of steroid biosynthesis, need to be confirmed using liquid chromatography-tandem mass spectrometry. Daily quality controls (QCs) for the 2nd-tier CAH assay are not commercially available and are therefore generally prepared within the laboratory. For the first time, we aimed to compare five different QC preparation approaches used in routine diagnostics for CAH on the concentrations of cortisol, 21-deoxycortisol, 11-deoxycortisol, 4-androstenedione and 17-hydroxyprogesterone in dried blood spots. The techniques from Prep1 to Prep5 were tested at two analyte concentrations by spiking aliquots of a steroid-depleted blood, derived from washed erythrocyte suspension and steroid-depleted serum. The preparation processes differed in the sequence of the preparation steps and whether freeze-thaw cycles were used to facilitate blood homogeneity. The five types of dried blood spot QCs were assayed and quantitated in duplicate on five different days using a single calibration row per day. Inter-assay variations less than 15% and concentrations within ±15% of the nominal values were considered acceptable. Results obtained by means of the four dried blood spot QC preparation techniques (Prep1, Prep2, Prep4 and Prep5) were statistically similar and remained within the ±15% ranges in terms of both reproducibility and nominal values. However, concentration results for Prep3 (spiking prior to three freeze-thaw cycles) were significantly lower than the nominal values in this setting, with differences exceeding the ±15% range in many cases despite acceptable inter-assay variations. These findings have implications for the in-house preparation of QC samples in laboratory developed tests for CAH, including 2nd-tier assays in newborn screening.


Subject(s)
Adrenal Hyperplasia, Congenital/blood , Adrenal Hyperplasia, Congenital/diagnosis , Dried Blood Spot Testing/methods , Neonatal Screening/methods , 17-alpha-Hydroxyprogesterone/blood , Androstenedione/blood , Cortodoxone/blood , Humans , Infant, Newborn , Tandem Mass Spectrometry
4.
J Chromatogr A ; 1635: 461775, 2021 Jan 04.
Article in English | MEDLINE | ID: mdl-33302138

ABSTRACT

Concurrent measurement of tyrosine, tryptophan and their metabolites, and other co-factors could help to diagnose and better understand a wide range of metabolic and neurological disorders. The two metabolic pathways are closely related to each other through co-factors, regulator molecules and enzymes. By using high performance liquid chromatography coupled to electrospray ionization triple quadrupole mass spectrometry, we present a robust, selective and comprehensive method to determine 30 molecules within 20 min using a Waters Atlantis dC18. The method was validated according to the guideline of European Medicines Agency on bioanalytical method validation. Analytical performance met all the EMA requirements and the assay covered the relevant clinical concentrations. Linear correlation coefficients were all >0.998. Intra-day and inter-day accuracy were between 80-119% and 81-117%, precision 1-19% respectively. The method was applied to measure TYR, TRP and their metabolites, and other neurologically important molecules in human serum and CSF samples. The assay can facilitate the diagnosis and is suitable for determination of reference values in clinical laboratories.


Subject(s)
Biomarkers/analysis , Clinical Chemistry Tests/methods , Tryptophan/analysis , Tyrosine/analysis , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Chromatography, High Pressure Liquid , Clinical Chemistry Tests/standards , Humans , Metabolic Networks and Pathways , Reproducibility of Results , Spectrometry, Mass, Electrospray Ionization , Tryptophan/blood , Tryptophan/cerebrospinal fluid , Tyrosine/blood , Tyrosine/cerebrospinal fluid
5.
PLoS One ; 15(5): e0233724, 2020.
Article in English | MEDLINE | ID: mdl-32470014

ABSTRACT

Congenital adrenal hyperplasia (CAH) is a severe inherited disorder of cortisol biosynthesis that is potentially lethal or can seriously affect quality of life. For the first time, we aimed to assess the stability of 21-deoxycortisol (21Deox), 11-deoxycortisol (11Deox), 4-androstenedione (4AD), 17-hydroxyprogesterone (17OHP) and cortisol (Cort), diagnostic for CAH, in dried blood spots (DBSs) during a 1 year storage at different temperatures. Spiked DBS samples were stored at room temperature, 4 °C, -20 °C or -70 °C, respectively and analyzed in triplicates using liquid chromatography-tandem mass spectrometry at Weeks 0, 1, 2, 3 and 4, Month 6 and Year 1. Analyte levels within ±15% vs the baseline were considered stable. Our observations show that 21Deox, 4AD and 17OHP were not significantly changed for 1 year even at room temperature at either analyte levels. In contrast, Cort required storage at 4 °C, -20 °C or -70 °C for long-term stability, being significantly decreased at room temperature from Month 6 (p<0.01) in both the 30(60) nM and the 90(180) nM samples. 11Deox was significantly decreased at room temperature at Year 1 (p<0.01) and only in the 30(60) nM samples. Thus, all biomarkers were stable for up to 1 year at 4 °C, -20 °C or -70 °C and at least for 4 weeks at room temperature. These findings have implications for analyses of stored DBS samples in 2nd-tier assays in newborn screening and for retrospective CAH studies.


Subject(s)
Adrenal Hyperplasia, Congenital/blood , Androstenediol/blood , Dried Blood Spot Testing , Mass Screening , Pregnenediones/blood , Preservation, Biological , Adrenal Hyperplasia, Congenital/diagnosis , Female , Humans , Infant, Newborn , Male
6.
Orv Hetil ; 158(48): 1909-1918, 2017 Dec.
Article in Hungarian | MEDLINE | ID: mdl-29172662

ABSTRACT

INTRODUCTION: Infant vitamin B12 deficiency can manifest as a severe neurodegenerative disorder and is usually caused by maternal deficiency due to vegetarian diet or pernicious anaemia. Its early recognition and treatment can prevent potentially serious and irreversible neurologic damage. Biochemically, vitamin B12 deficiency leads to an accumulation of methylmalonic acid, homocysteine, and propionylcarnitine. Expanded newborn screening using tandem mass spectrometry may identify neonatal and maternal vitamin B12 deficiency by measurement of propionylcarnitine and other metabolites in the dried blood spot sample of newborns. AIM: To summarize our experiences gained by screening for vitamin B12 deficiency. METHOD: Clinical and laboratory data of vitamin B12-deficient infants diagnosed in Szeged Screening Centre were retrospectively analysed. RESULTS: In Hungary, expanded newborn screening was introduced in 2007. Since then approximately 395 000 newborns were screened in our centre and among them, we identified four newborns with vitamin B12 deficiency based on their screening results. In three cases an elevated propionylcarnitine level and in the fourth one a low methionine level were indicative of vitamin B12 deficiency. We also detected an additional vitamin B12-deficient infant with neurological symptoms at 4 months of age, after a normal newborn screening, because of elevated urinary methylmalonic acid concentration. Vitamin B12 deficiency was secondary to maternal autoimmune pernicious anaemia in all the five infants. As a result of the recognized cases the incidence of infant vitamin B12 deficiency in the East-Hungarian region was 1.26/100 000 births, but the real frequency may be higher. Conslusions: Optimizing the cut off values of current screening parameters and measuring of methylmalonic acid and/or homocysteine in the dried blood spot, as a second tier test, can improve recognition rate of vitamin B12 deficiency. Orv Hetil. 2017; 158(48): 1909-1918.


Subject(s)
Neonatal Screening/methods , Pregnancy Complications/diagnosis , Vitamin B 12 Deficiency/diagnosis , Anemia, Pernicious/immunology , Female , Humans , Hungary , Incidence , Infant, Newborn , Maternal Nutritional Physiological Phenomena , Pregnancy , Retrospective Studies , Tandem Mass Spectrometry , Vitamin B 12 Deficiency/blood , Vitamin B 12 Deficiency/etiology , Vitamin B 12 Deficiency/urine
7.
PLoS One ; 12(9): e0184897, 2017.
Article in English | MEDLINE | ID: mdl-28915261

ABSTRACT

BACKGROUND AND AIMS: Increased propionylcarnitine levels in newborn screening are indicative for a group of potentially severe disorders including propionic acidemia (PA), methylmalonic acidemias and combined remethylation disorders (MMACBL). This alteration is relatively non-specific, resulting in the necessity of confirmation and differential diagnosis in subsequent tests. Thus, we aimed to develop a multiplex approach for concurrent determination of 3-hydroxypropionic acid, methylmalonic acid and methylcitric acid from the same dried blood spot (DBS) as in primary screening (second-tier test). We also set out to validate the method using newborn and follow-up samples of patients with confirmed PA or MMACBL. METHODS: The assay was developed using liquid chromatography-tandem mass spectrometry and clinically validated with retrospective analysis of DBS samples from PA or MMACBL patients. RESULTS: Reliable determination of all three analytes in DBSs was achieved following simple and fast (<20 min) sample preparation without laborious derivatization or any additional pipetting steps. The method clearly distinguished the pathological and normal samples and differentiated between PA and MMACBL in all stored newborn specimens. Methylcitric acid was elevated in all PA samples; 3-hydroxypropionic acid was also high in most cases. Methylmalonic acid was increased in all MMACBL specimens; mostly together with methylcitric acid. CONCLUSIONS: A liquid chromatography-tandem mass spectrometry assay allowing simultaneous determination of the biomarkers 3-hydroxypropionic acid, methylmalonic acid and methylcitric acid in DBSs has been developed. The assay can use the same specimen as in primary screening (second-tier test) which may reduce the need for repeated blood sampling. The presented preliminary findings suggest that this method can reliably differentiate patients with PA and MMACBL in newborn screening. The validated assay is being evaluated prospectively in a pilot project for extension of the German newborn screening panel (?Newborn screening 2020"; Newborn Screening Center, University Hospital Heidelberg).


Subject(s)
Amino Acid Metabolism, Inborn Errors/blood , Citrates/blood , Dried Blood Spot Testing/methods , Lactic Acid/analogs & derivatives , Mass Screening/methods , Methylmalonic Acid/blood , Propionic Acidemia/blood , Chromatography, Liquid/methods , Female , Humans , Infant, Newborn , Lactic Acid/blood , Male , Mass Spectrometry/methods
8.
Hemodial Int ; 15(4): 501-8, 2011 Oct.
Article in English | MEDLINE | ID: mdl-22111818

ABSTRACT

The relationship between renal disease progression and genetic polymorphism of enzymes influencing endothelial function remains incompletely understood. We genotyped three cohorts of elderly Hungarian patients: 245 patients with end-stage renal disease (ESRD) on chronic hemodialysis (HD), 88 patients with mild chronic kidney disease (CKD), and 200 healthy controls. The underlying diagnoses of renal diseases were primary glomerulonephritis, interstitial nephritis, hypertension, diabetic nephropathy, and hereditary diseases. We examined genetic polymorphisms of eight candidate genes associated with endothelial function: endothelial constitutive nitric oxide synthase (ecNOS) T-786C, endothelin-1 G5727T, methylenetetrahydrofolate reductase (MTHFR) C677T, paraoxonase-1 Q192R and M55L, angiotensinogen M235T, angiotensin-converting enzyme (ACE) I/D and angiotensin II type 1 receptor A1166C gene. Six gene polymorphisms were detected by real-time polymerase chain reaction with melting-point analysis, and two via allele-specific amplification and gel electrophoresis. Control group patients were in Hardy-Weinberg equilibrium for all tested genotypes. In ESRD patients attributed to hypertension, the endothelin gene G5727T GG genotype occurred significantly less but GT genotype more frequently (P < 0.01 for both). In ESRD patients attributed to primary glomerulonephritis, more ACE DD and less ID genotypes were found (P < 0.02 for both) than in the controls. The underlying diagnosis may modify the association of genetic polymorphism and dialysis-dependent ESRD.


Subject(s)
Kidney Failure, Chronic/genetics , Kidney Failure, Chronic/therapy , Polymorphism, Genetic , Renal Dialysis , Adult , Aryldialkylphosphatase/genetics , Endothelin-1/genetics , Female , Humans , Hungary/epidemiology , Kidney Failure, Chronic/mortality , Male , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Middle Aged , Nitric Oxide Synthase Type III/genetics , Peptidyl-Dipeptidase A/genetics , Risk Factors
9.
Int J Pediatr Obes ; 6(2-2): e318-25, 2011 Jun.
Article in English | MEDLINE | ID: mdl-20883102

ABSTRACT

OBJECTIVE: Apolipoprotein A5 (APOA5) gene variants have been shown to be associated with elevated TG levels; the T-1131C (rs662799) variant has been reported to confer risk for the metabolic syndrome in adult populations. Little is known about the APOA5 variants in pediatric population, no such information is available for pediatric obesity at all. Here we examined four haplotype-tagging polymorphisms (T-1131C, IVS3 + G476A [rs2072560], T1259C [rs2266788] and C56G [rs3135506]) and studied also the frequency of major naturally occurring haplotypes of APOA5 in obese children. METHODS: The polymorphisms were analyzed in 232 obese children, and in 137 healthy, normal weight controls, using PCR-RFLP methods. RESULTS: In the pediatric patients we could confirm the already known adult subjects based association of -1131C, IVS3 + 476A and 1259C variants with elevated triglyceride concentrations, both in obese patients and in the controls. The prevalence of the APOA5*2 haplotype (containing the minor allele of T-1131C, IVS3 + G476A and T1259C SNPs together) was 15.5% in obese children, and 5.80% in the controls (p<0.001); multiple logistic regression analysis revealed that this haplotype confers susceptibility for development of obesity (OR=2.87; 95% CI: 1.29-6.37; p≤0.01). By contrast, the APOA5*4 haplotype (with -1131C alone) did not show similar associations. Our findings also suggest that the APOA5*5 haplotype (1259C alone) can be protective against obesity (OR=0.25; 95% CI: 0.07-0.80; p<0.05). CONCLUSIONS: While previous studies in adults demonstrated, that the APOA5 -1131C minor allele confers risk for adult metabolic syndrome, here we show, that the susceptibility nature of this SNP restricted to the APOA5*2 haplotype in pediatric obese subjects.


Subject(s)
Apolipoproteins A/genetics , Obesity/genetics , Polymorphism, Single Nucleotide , Adolescent , Apolipoprotein A-V , Biomarkers/blood , Body Mass Index , Case-Control Studies , Chi-Square Distribution , Cholesterol/blood , Female , Gene Frequency , Genetic Predisposition to Disease , Haplotypes , Humans , Hungary , Logistic Models , Male , Obesity/blood , Odds Ratio , Phenotype , Polymerase Chain Reaction , Risk Assessment , Risk Factors , Triglycerides/blood
10.
Eur J Pediatr ; 169(11): 1369-74, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20552222

ABSTRACT

UNLABELLED: The microvascular responses to endothelium-dependent vasodilators (e.g., acetylcholine), endothelium-independent vasodilators (e.g., sodium nitroprusside), and to local heating were studied (for the first time) in adolescents with essential hypertension, grouped according to their body mass index. The forearm microvascular reactivities of thirty-three hypertensive adolescents (ten lean, 13 overweight, and ten obese) and 19 healthy controls were assessed by means of laser Doppler flowmetry. Blood levels of enzymatic and nonenzymatic antioxidants and malondialdehyde were determined. The perfusion increments in response to acetylcholine iontophoresis were not significantly attenuated in the patient groups as compared with the controls. Sodium nitroprusside (SNP) iontophoresis resulted in significantly smaller perfusion increments in the lean and obese hypertensives than in the controls (both p < 0.05). Similar responses to local heating (44°C) performed after either acetylcholine or SNP iontophoresis were observed at the respective measurement sites. As compared with the controls, we found elevated ratios of the whole blood oxidized and reduced glutathione in all the patient groups (all p < 0.001), increased erythrocyte catalase activities in the overweight hypertensives (p < 0.05), and decreased ratios of the plasma alpha-tocopherol and triglycerides in the obese hypertensive group (p < 0.05). CONCLUSION: The endothelium-dependent microvascular reactivity was not significantly attenuated in the hypertensive adolescents in contrast with the impaired endothelium-independent vasorelaxation in the lean and obese hypertensives.


Subject(s)
Hypertension/complications , Microcirculation/physiology , Obesity/physiopathology , Overweight/physiopathology , Thinness/physiopathology , Adolescent , Blood Pressure , Child , Female , Follow-Up Studies , Humans , Hypertension/blood , Hypertension/physiopathology , Laser-Doppler Flowmetry , Male , Malondialdehyde/blood , Obesity/blood , Obesity/complications , Overweight/blood , Overweight/complications , Oxidative Stress , Prognosis , Risk Factors , Thinness/blood , Thinness/complications , Vasodilation/physiology , Young Adult
11.
Kidney Blood Press Res ; 31(1): 63-9, 2008.
Article in English | MEDLINE | ID: mdl-18259097

ABSTRACT

BACKGROUND/AIMS: Blood pressure (BP) during childhood is an established predictor of adult BP, which in turn predicts mortality in the event of cardiovascular disease. Reference data for systolic (SBP) and diastolic (DBP) BP are not available for Hungarian children (aged 11-14 years). The aim was to make up for this deficit. METHODS: Analyses were performed on 14,504 Hungarian children aged 11-16 years. All measurements were made with a validated, automated device. Criteria described by international guidelines were used. RESULTS: The 50th, 90th and 95th percentile BP values were defined by dividing the participating population into age-, gender- and height-specific subgroups. The SBP increased linearly with age to an apparent plateau at around the age of 15-16 years in both girls and boys, and there were similar increases in DBP and mean arterial pressure. Both the SBP and DBP revealed highly significant correlations in both genders with weight (SBP: r = 0.452, p < 0.01; DBP: r = 0.340, p < 0.01), height (SBP: r = 0.314, p < 0.01; DBP: r = 0.245, p < 0.01) and body mass index (SBP: r = 0.407, p < 0.01; DBP: r = 0.294, p < 0.01). CONCLUSION: The present study provides reference data on SBP and DBP, facilitating the diagnosis of essential hypertension in the 11- to 16-year age group.


Subject(s)
Blood Pressure/physiology , Adolescent , Age Factors , Body Height/physiology , Child , Diastole/physiology , Female , Humans , Hungary/epidemiology , Hypertension/diagnosis , Hypertension/epidemiology , Hypertension/physiopathology , Male , Reference Values , Sex Factors , Systole/physiology
12.
Kidney Blood Press Res ; 29(3): 144-51, 2006.
Article in English | MEDLINE | ID: mdl-16912512

ABSTRACT

BACKGROUND/AIMS: Paraoxonase 1 (PON1) is associated with high-density lipoproteins in the plasma, and is capable of hydrolysing oxidized lipids and preventing the oxidation of low-density lipoproteins. Oxidative stress and the PON1 (activity and Q192R polymorphism) were analysed in adolescent patients with essential (n = 49) or obesity-induced hypertension (n = 79), uraemic patients (n = 20), and also in obese normotensive patients (n = 60) and age-matched controls (n = 57). METHODS: The PON1 activity was measured via paraoxon hydrolysis. The PON1 genotype was determined by real-time PCR. The levels of oxidized and reduced glutathione, the end-products of nitric oxide, cysteine, homocysteine and lipid peroxidation in the plasma were measured and related to the PON1 status. RESULTS: There were no significant differences between the patient groups and the control group in the genotype distributions and the allele frequencies of the Q192R polymorphism. The PON activity was significantly lower (p < 0.001) in the uraemic hypertensive group than in the controls. The MDA concentration was significantly higher in the uraemic hypertensive (p < 0.001) and obese hypertensive (p < 0.05) patients. The plasma NOx concentrations were significantly lower (p < 0.001) and the ratio MDA/NOx were significantly higher in all four patient groups. The GSH levels were significantly lower in the patients with hypertension (p < 0.001) and obesity-induced hypertension (p < 0.05) than in the controls, while the GSSG level (p < 0.01) and the ratio GSSG/GSH (p < 0.05) was significantly higher in the uraemic hypertensive group. The plasma homocysteine level was significantly higher (p < 0.001) in the uraemic hypertensive patients as compared with the controls. CONCLUSIONS: We found no significant correlation between the biochemical parameters and neither genotypes nor enzyme activities. The PON1 status and the levels of certain biochemical parameters are independently associated with the hypertension in hypertensive and obese hypertensive patients, and the elevated levels of lipid peroxides and plasma homocysteine may contribute to the increased risk of cardiovascular complications in patients on haemodialysis.


Subject(s)
Aryldialkylphosphatase/metabolism , Hypertension/physiopathology , Obesity/physiopathology , Oxidative Stress/physiology , Uremia/physiopathology , Adolescent , Analysis of Variance , Aryldialkylphosphatase/genetics , Female , Glutathione/analysis , Homocysteine/blood , Humans , Hypertension/etiology , Lipid Peroxides/blood , Male , Obesity/complications , Polymorphism, Genetic , Renal Dialysis
13.
Pediatr Nephrol ; 21(10): 1419-25, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16896999

ABSTRACT

Obesity-induced hypertension and essential hypertension in lean patients are two different forms of hypertension. The main goal of this study was to test whether there are differences in biochemical parameters between subjects with obesity-associated hypertension and those with essential hypertension. We examined whether the biochemical responses to angiotensin-converting enzyme inhibitor (ACEI) ramipril therapy reveal properties of these two conditions that might explain the differences in clinical outcome. Before ramipril therapy, the hypertensive group exhibited increases in ACE activity (p<0.05), plasma malondialdehyde (MDA) concentration and the malondialdehyde/nitric oxide end-product ratio (MDA/NO(x)) (p<0.05), and decreases in xanthine oxidase (XO) activity (p<0.05) and plasma nitric oxide end-product (NO(x)) level (p<0.01). Before medication, plasma endothelin-1 (ET-1), plasma leptin, and leptin receptor levels were normal. Following ramipril treatment, ACE activity normalized. Before ACE inhibitor treatment, the obese-hypertensive group exhibited elevated levels of plasma ET-1 (p<0.05), plasma leptin (p<0.01), XO activity (p<0.05), plasma MDA and MDA/NO(x) (p<0.05), and reduced levels of plasma NO(x)(p<0.01) and leptin receptors (p<0.001). Following medication, the plasma NO(x) level, MDA/NO(x), and XO activity returned to normal while ACE activity decreased (p<0.001). In patients with essential hypertension, NO availability and ACE activity, and in those with obesity-associated hypertension, hyperleptinemic effects, NO level, endothelin-1 concentration and XO activity, may be important factors in the pathology.


Subject(s)
Hypertension/etiology , Hypertension/physiopathology , Obesity/complications , Obesity/physiopathology , Adolescent , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Body Mass Index , Endothelin-1/blood , Endothelin-1/physiology , Female , Humans , Hypertension/blood , Hypertension/drug therapy , Leptin/blood , Leptin/physiology , Male , Malondialdehyde/blood , Nitric Oxide/blood , Nitric Oxide/physiology , Obesity/blood , Peptidyl-Dipeptidase A/blood , Peptidyl-Dipeptidase A/physiology , Ramipril/therapeutic use , Xanthine Oxidase/blood , Xanthine Oxidase/physiology
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