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- Sverrisdóttir, Yrsa Bergmann, 1960, et al.
(författare)
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The effect of growth hormone (GH) replacement therapy on sympathetic nerve hyperactivity in hypopituitary adults: a double-blind, placebo-controlled, crossover, short-term trial followed by long-term open GH replacement in hypopituitary adults.
- 2003
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Ingår i: Journal of hypertension. - 0263-6352. ; 21:10, s. 1905-14
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Tidskriftsartikel (refereegranskat)abstract
- To test whether sympathetic nerve hyperactivity associated with adult hypopituitarism and untreated growth hormone (GH) deficiency is affected by GH treatment.Sympathetic nerve activity to the muscle vascular bed (MSA) expressed as burst frequency (bursts/min) and incidence (bursts/100 heartbeats) was recorded in 10 hypopituitary patients (aged 48-69 years), before and after acute (1 week) randomized, double-blind, crossover treatment with a 1-month washout period and chronic (1 year) GH replacement treatment.MSA burst frequency and incidence remained unchanged from baseline values after the short-term treatment, but exhibited decreases in median values [from 53 to 47 bursts/min (P = 0.02) and from 85 to 70 bursts/100 heartbeats (P = 0.03), respectively] after 12 months of replacement therapy. Twenty-four-hour urinary excretion of nitrate increased after the short-term cross-over treatment and the long-term treatment (P = 0.04). Diastolic blood pressure and waist circumference decreased after the 12-month treatment (P = 0.02 and P = 0.04, respectively). No correlation was found between the reduction in MSA and the increase in 24-h urinary nitrate excretion, the decrease in diastolic blood pressure and waist circumference.The sympathoexcitation in adult GH deficiency and the modest decline in MSA seen after long-term GH replacement treatment may suggest that the somatotropic axis is involved in the regulation of central sympathetic outflow.
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- Söderling, Ann-Sofi, et al.
(författare)
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A derivatization assay using gaschromatography/negative chemical ionization tandem mass spectrometry to quantify 3-nitrotyrosine in human plasma
- 2003
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Ingår i: J Mass Spectrom. ; 38:11
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Tidskriftsartikel (refereegranskat)abstract
- Endogenous free or protein-associated 3-nitrotyrosine (3-NT) has been proposed as a biomarker of in vivo oxidative damage caused by nitrating agents. Isotopic dilution assay gaschromatographic/mass spectrometric (GC/MS) techniques have been employed to measure endogenous 3-NT levels. However, the quantitative normal plasma values reported so far are inconsistent. The results vary between the assays; they may have been influenced by in vitro artifactual nitration of tyrosine to 3-NT. In this study, a simple and artifact-free derivatization method for quantifying the endogenous 3-NT content of biological samples by GC/negative chemical ionization MS/MS is presented. The method is based on reduction of the nitro group of the molecule by dithionite, heptafluorobutyric acylation and subsequent methyl derivatization, di-O-methyldi-N-heptafluorobutyryl being the major derivative. The results showed excellent GC and MS properties, such as low background and a favorable fragmentation pattern. Endogenous 3-NT was unequivocally quantified using collision-induced dissociation in the selected reaction monitoring mode, whereas co-elution of unknown compounds interfered in the selected-ion monitoring mode. We found that tyrosine was nitrated in the presence of nitrate anions and heptafluorobutyric anhydride, but the product appeared as a di-O-methylmono-N-heptafluorobutyryl derivative. Therefore, artifactually formed 3-NT did not contribute to the measured endogenous 3-NT level owing to its different derivative structure. The method was applied to determine endogenous 3-NT in human plasma and plasma proteins. A detection limit of 0.03 nM for (13)C(6)-labeled 3-NT in plasma samples was established and the response was linear over a concentration range of 0-50 nM (R(2) > 0.999). The endogenous free 3-NT level (mean +/- SD) in ultrafiltered plasma samples from 12 healthy adults was 0.74 +/- 0.30 nM. The mean concentration of 3-NT in their plasma total proteins was 0.60 +/- 0.40 pmol mg(-1). Hence, the described method is selective, eliminates the problem of artifactual nitration and is feasible for the quantification of free and protein-associated 3-NT in biological samples such as plasma.
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