Biomedical subjects

J Dötsch

Publications and source records attributed to J Dötsch.

At least 37 records · Page 2Linked to original sources

PubMed2001

Persistent improvement of gas exchange and lung mechanics by aerosolized perfluorocarbon.

The effect of aerosolized perfluorocarbon (PFC) (FC77) on pulmonary gas exchange and lung mechanics was studied in a surfactant depleted piglet model. Sixty minutes after induction of lung injury by bronchoalveolar lavage, 20 piglets were randomized to receive aerosolized PFC (Aerosol-PFC, 10 ml/kg/h, n = 5), partial liquid ventilation (PLV) at FRC capacity volume (FRC-PLV, 30 ml/kg, n = 5) or low volume (LV-PLV, 10 ml/kg/h, n = 5), or intermittent mandatory ventilation (IMV) (Control, n = 5). After 2 h, perfluorocarbon application was stopped and IMV was continued for 6 h. Sixty minutes after the onset of therapy, PaO2 was significantly higher and PaCO2 was significantly lower in the Aerosol-PFC and the FRC-PLV groups than in the LV-PLV and the Control groups; p < 0.001. Six hours after treatment, maximum PaO2 was found in the Aerosol-PFC group: 406.4 +/- 26.9 mm Hg, FRC-PLV: 217.3 +/- 50.5 mm Hg, LV-PLV: 96.3 +/- 18.9 mm Hg, Control: 67.6 +/- 8.4 mm Hg; p < 0.001. PaCO2 was lowest in the Aerosol-PFC group: 24.2 +/- 1.7 mm Hg, FRC-PLV: 35.9 +/- 2.8 mm Hg, LV-PLV: 56.7 +/- 12.4 mm Hg, Control: 60.6 +/- 5.1 mm Hg; p < 0.01. Dynamic compliance (C20/c) was highest in the Aerosol-PFC group; p < 0.01. Aerosolized perfluorocarbon improved pulmonary gas exchange and lung mechanics as effectively as PLV did in surfactant-depleted piglets, and the improvement was sustained longer.

Aerosols↗

PubMed2001

Effect of glucocorticoid excess on the cortisol/cortisone ratio.

OBJECTIVE: The conversion of cortisol, which binds avidly to the mineralocorticoid receptor, to cortisone, which no longer has mineralocorticoid function, is predominantly catalyzed by the 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD 2). It was the objective of the present study to examine the impact of different forms of glucocorticoid excess on the cortisol/cortisone ratio and to differentiate their role in the genesis of hypertension. DESIGN AND METHODS: Plasma cortisol and cortisone levels were determined in 12 adults with Cushing's disease, 12 adults with hypercortisolism due to an adrenal tumor, and 20 healthy volunteers before and after an intravenous ACTH test, using specific radioimmunoassays after automated Sephadex LH 20 chromatography. RESULTS: The cortisol/cortisone ratios were significantly higher in patients with Cushing's disease (13.9 +/- 1.1), adrenal tumors (11.5 +/- 2.3), and in healthy volunteers after ACTH stimulation (14.1 +/- 2.0) than in untreated controls (6.0 +/- 0.5) (P < 0.001, P < 0.05, and P < 0.001, respectively). Similar differences were seen for cortisol plasma concentrations, whereas cortisone concentrations did not differ among the groups. CONCLUSIONS: Our data suggest that the excessive mineralocorticoid effects in patients with hypercortisolism are inflicted by elevated cortisol/cortisone ratios possibly due to an insufficient conversion of cortisol to cortisone by 11beta-HSD 2. This may provide a possible explanation for the occurrence of hypertension. This effect seems to be independent of the role of ACTH in the mechanism of hypercortisolism.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed2001

Increase of endothelial nitric oxide synthase and endothelin-1 mRNA expression in human placenta during gestation.

OBJECTIVE: To investigate the maturation of the paracrine system's endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), endothelin-1 (ET-1) and adrenomedullin (AM) in human placenta during the 2nd and 3rd trimester of pregnancy. STUDY DESIGN: Placental tissue from 14 healthy women with normal pregnancy and from 13 patients giving birth to premature infants following premature labor was obtained. Messenger RNA expression was determined using quantitative TaqMan real-time PCR. RESULTS: Placental eNOS/GAPDH and ET-1/GAPDH mRNA expression significantly increased as a function of gestational age (r=0.63, P<0.001 and r=0.53, P=0.007, respectively). There was no change in gene expression of neither iNOS nor AM mRNA/GAPDH during gestation (r=0.02, P=0.75 and r=0.001, P=0.99, respectively). CONCLUSION: There is a maturation of eNOS and ET-1 in human placenta with gestation reflecting developmental changes of important paracrine endothelial and trophoblastic regulators. AM and iNOS show no maturation during pregnancy.

Adrenomedullin↗

PubMed2001

Gene expression of adrenomedullin, leptin, their receptors and neuropeptide Y in hormone-secreting and non-functioning pituitary adenomas, meningiomas and malignant intracranial tumours in humans.

The aim of this study was to assess human intracranial tumours for their gene expression pattern of the vasoactive peptide adrenomedullin (AM), its receptor (AM-R) and leptin, which exerts multiple biological effects including proliferation and angiogenesis via the leptin receptor (OB-Rb). Gene activity of neuropeptide Y (NPY) was monitored additionally. We investigated whether there was a characteristic gene expression pattern of AM and leptin in different intracranial tumours, depending on their proliferation activity and biological behaviour. We investigated 35 non-functioning pituitary adenomas (including eight null cell, four silent plurihormonal, 23 silent gonadotroph adenomas), seven somatotropinomas, seven prolactinomas, eight meningiomas, five astrocytomas, two glioblastoma multiformes and unaffected temporal lobe (n = 8). Quantitative reverse transcriptase-polymerase chain reaction (TaqMan RT-PCR) was performed. AM mRNA was detectable in all tumour specimens. AM/GAPDH (glyceraldehyde-3-phosphate dehydrogenase) ratio was significantly higher in somatotropinomas, as was AM/CD31 ratio in prolactinomas, compared with inactive adenomas (P < 0.05). AM-R mRNA was found in all tumour subgroups in small quantities but, in general, higher in tumours than in temporal lobe tissue, respectively. AM-R/CD31 ratio was significantly higher in prolactinomas than in inactive adenomas (P < 0.05). Leptin was detectable in very low quantities in each subgroup. OB-Rb gene expression was found in all tumour subgroups, OB-Rb/GAPDH ratio was highest for meningiomas (P < 0.0001, compared with temporal lobe). NPY mRNA was detectable in temporal lobe in higher quantities than in tumours (P < 0.0001), and almost undetectable in prolactinomas and astrocytomas. Our data demonstrate that AM and AM-R, NPY, as well as leptin and OB-Rb, are expressed in various intracranial tumours in humans but their particular function has to be elucidated further. At present, there is no evidence for a cross-talk on transcriptional level between the peptidergic vasodilative system AM and the putative angiogenic and proliferation affecting factor leptin.

Adenoma↗

PubMed2001

Hypercalcemia and idiopathic hypoparathyroidism.

Idiopathic primary hypoparathyroidism (prHP) is a rare disorder and clinical experience of its management is limited. Prolonged immobilization of such patients can cause hypercalcemia and hypercalciuria. We report on a boy with prHP who developed hypercalcemia and renal failure as a result of calcium and calcitriol substitution not being stopped while he was immobilized for 2 months. Any substitution in patients with prHP must be stopped during prolonged immobilization. Laboratory monitoring is mandatory during this period.

Calcium↗

PubMed2001

Increased endothelin-1 and decreased adrenomedullin gene expression in the stenotic tissue of congenital pelvi-ureteric junction obstruction in children.

OBJECTIVES: To test the hypothesis that the gene expression of endothelin-1 and adrenomedullin may be altered in stenotic tissues of patients with congenital hydronephrosis caused by pelvi-ureteric junction (PUJ) obstruction. MATERIALS AND METHODS: Using real-time reverse transcription-polymerase chain reaction, mRNA of smooth muscle-constricting endothelin-1 and of smooth muscle-relaxing adrenomedullin was quantified in tissue specimens of 20 patients with PUJ obstruction (mean age 5.1 years, SD 7.0) and of 21 controls with normal PUJs (mean age 23.5 years, SD 24.2). RESULTS: The amount of endothelin-1 mRNA in stenotic specimens was higher than in the controls, indicated by significantly lower threshold cycles (Ct values) in real-time PCR for the target gene in the obstructive tissue, with mean (SD) values of 24.9 (1.6) and 26.0 (2.1) (P < 0.05), respectively. The endothelin-1/CD31 ratio was significantly higher in the patients (P < 0.05) than in controls. In addition, adrenomedullin gene expression in the obstructed junctions was significantly lower than in normal junctions, with higher Ct values for the patient group of 26.7 (1.6) vs 25.2 (1.8) (P < 0.05) and lower adrenomedullin mRNA when standardized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (P < 0.05), CD31 (P < 0.01) and smooth muscle alpha-actin mRNA (P < 0.01). The two groups showed no significant differences for GAPDH and CD31 mRNA content, whereas there was about twice as much alpha-actin mRNA in stenotic tissues than in unaffected PUJs, shown by the lower Ct values for the patient group of 16.9 (2.0) vs 17.9 (2.6) (P < 0.05). Furthermore, endothelin-1, adrenomedullin and alpha-actin mRNA amounts were independent of age. CONCLUSION: Taken together these results provide evidence that the production of autocrine/paracrine acting endothelin-1 and adrenomedullin is altered in tissues of patients with genuine PUJ obstruction, and may be involved in the pathogenesis of congenital hydronephrosis.

Adolescent↗

PubMed2001

Identification of leptin in human saliva.

Leptin is produced predominantly in adipose tissue but has recently also been found in gastric mucosa. It has been shown that the oral application of leptin induces neuronal activity in the brain stem of rodents. The objective of the present study was to identify this hormone in human saliva and to examine the production and stability of salivary leptin. We have demonstrated production of leptin in salivary glands and oral mucosa by RT-PCR, its storage by immunocytochemistry, and the release of the peptide by RIA. Chromatographic analysis and immunoblotting confirmed the identity of leptin. There is a strong linear correlation (r2 = 0.78) between leptin concentrations from simultaneously collected saliva and plasma samples (n = 61). Stimulation of saliva flow increases total leptin secretion up to 3-fold (P < 0.001). As to the stability of leptin in gastric fluid, we found the peptide was not degraded above pH 3.5. Additionally, salivary leptin remains stable up to 5 d at 4 C. With regard to the presence of leptin receptors in gastric mucosa, we suggest salivary leptin as being a possible ligand for gastric leptin receptors. Furthermore, the determination of leptin in saliva allows for noninvasive sample collection.

Adult↗

PubMed2001

Decreased gene expression of 11beta-hydroxysteroid dehydrogenase type 2 and 15-hydroxyprostaglandin dehydrogenase in human placenta of patients with preeclampsia.

Cortisol reduces the activity of the PG-inactivating enzyme 15-hydroxyprostaglandin dehydrogenase (PGDH) in human placental cells. The objective was to investigate a possible relation between 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), converting cortisol to cortisone, and PGDH gene expression in the placenta of patients with preeclampsia. In placental tissue taken from 20 healthy women with normal pregnancy, 20 premature babies born after labor before term, and 18 neonates after preeclamptic pregnancy, 11beta-HSD2 and PGDH messenger RNA (mRNA) expression was determined using quantitative TaqMan real-time PCR and quantitative competitive PCR. When comparing matched pairs, there were 3-fold lower 11beta-HSD2/glyceraldehyde-3-phosphate dehydrogenase (11beta-HSD2/GAPDH) mRNA levels in placentas of patients with preeclampsia than in controls [0.18 +/- 0.04 relative units (RU) and 0.61 +/- 0.10 RU, P = 0.0003]. We also found a 2-fold reduction in placental PGDH/GAPDH mRNA concentrations (0.28 +/- 0.15 RU and 0.50 +/- 0.18 RU, P = 0.0003). PGDH and 11beta-HSD2 mRNA levels correlated significantly (r = 0.66, P < 0.0001). In term placenta, 11beta-HSD2/GAPDH, but not PGDH, showed a significant correlation to birth weight (r = 0.43, P = 0.01) and to placental weight (r = 0.47, P = 0.01). Results could be confirmed by competitive PCR. We conclude that, in preeclampsia, 11beta-HSD2 mRNA expression is reduced, leading to the known decrease of 11beta-HSD2 activity. By means of an autocrine or paracrine mechanism, the diminished conversion of placental cortisol may lead to reduced PGDH mRNA expression as found in the present study.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed2001

Course of placental 11beta-hydroxysteroid dehydrogenase type 2 and 15-hydroxyprostaglandin dehydrogenase mRNA expression during human gestation.

BACKGROUND: During human pregnancy, 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) plays an important role in protecting the fetus from high maternal glucocorticoid concentrations by converting cortisol to inactive cortisone. Furthermore, 11beta-HSD2 is indirectly involved in the regulation of the prostaglandin inactivating enzyme 15-hydroxyprostaglandin dehydrogenase (PGDH), because cortisol reduces the gene expression and enzyme activity of PGDH in human placental cells. OBJECTIVE: To examine developmental changes in placental 11beta-HSD2 and PGDH gene expression during the 2nd and 3rd trimesters of human pregnancies. METHODS: In placental tissue taken from 20 healthy women with normal pregnancy and 20 placentas of 17 mothers giving birth to premature babies, 11beta-HSD2 and PGDH mRNA expression was determined using quantitative real-time PCR. RESULTS: Placental mRNA expression of 11beta-HSD2 and PGDH increased significantly with gestational age (r=0.55, P=0.0002 and r=0.42, P=0.007). In addition, there was a significant correlation between the two enzymes (r=0.58, P<0.0001). CONCLUSIONS: In the course of pregnancy there is an increase in 11beta-HSD2 and PGDH mRNA expression in human placental tissue. This adaptation of 11beta-HSD2 prevents increasing maternal cortisol concentrations from transplacental passage and is exerted at the gene level. 11beta-HSD2 up-regulation may also lead to an increase in PGDH mRNA concentrations that, until term, possibly delays myometrial contractions induced by prostaglandins.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗

PubMed2001

Renal loss of leptin in patients with nephrotic syndrome.

OBJECTIVE: In humans, short term changes of serum leptin lead to alterations in food intake and energy expenditure. The objective of the present study was to relate urine leptin concentrations with the extent of proteinuria in patients with nephrotic syndrome (NS). A second goal was to investigate the impact of potential urinary leptin losses on serum leptin concentrations and body composition. DESIGN AND METHODS: Seventeen patients with proteinuria were compared with twenty patients with remission of NS and ten healthy children. Leptin was measured by radioimmunoassay. RESULTS: Urinary leptin excretion in proteinuric patients was significantly higher than in non-proteinuric patients with and without NS and in healthy controls (2.64+/-0.034 microg/g creatinine, 0.026+/-0.05 microg/g creatinine, and 0.073+/-0.11 microg/g creatinine respectively; P<0.001 and P<0.01 respectively compared with controls). Urine leptin positively correlated with urine IgG concentration (P=0.013, r2=0.36) in the proteinuric group. No difference in serum leptin values could be demonstrated between the three groups. CONCLUSIONS: In summary, our data demonstrate a significant leptin excretion in children with severe proteinuria. Proteinuria, however, does not lead to changes in serum leptin, suggesting that the significant loss of leptin is compensated for by sustained up-regulation of leptin production.

Adolescent↗

PubMed2001

Unmasking of childhood hypothyroidism by disseminated xanthomas.

Secondary hyperlipidemia is a common laboratory finding in children with nephrotic syndrome, diabetes mellitus, and hypothyroidism. However, clinical signs of hyperlipidemia are extremely rare in childhood. We report on an 11-year-old girl who presented with a disseminated yellow papulomatous rash on the lower limbs and yellow skin creases on the palms of her hands. Blood tests yielded an opaque serum with a triglyceride concentration of 820 mg/dL and cholesterol of 1050 mg/dL. Skin biopsy of one of the papules confirmed the diagnosis of xanthomas. Additional examinations revealed clinical (weight gain, diminished growth rate) and biochemical primary hypothyroidism (free T4: 0.4 ng/L [normal 8-22 ng/L]; thyroid-stimulating hormone: >200 mU/L) as a consequence of Hashimoto thyroiditis (thyroid peroxidase and thyroglobulin: 4400 U/mL and >2000 U/mL, respectively; normal <60 U/mL). The patient was started on L-thyroxine, which led to a gradual decline of cholesterol and triglycerides to normal concentrations and a complete remission from the xanthomatous rash. For the first time, this case depicts disseminated xanthomas of the skin as the presenting complaint of severe hypothyroidism. hyperlipidemia, hypothyroidism, xanthoma.

Child↗

PubMed2001

Diagnostic and scientific applications of TaqMan real-time PCR in neuroblastomas.

This review summarizes the present data on the diagnostic and scientific applications of TaqMan real-time PCR in neuroblastomas, a novel fluorescence-based method for quantitation of gene expression and gene copy number variations as gene amplification and locus haploinsufficiencies. Particular emphasis is spent on precision and accuracy and the comparison of TaqMan real-time PCR with more traditional methods for quantitative PCR. Provided a proper assessment for each new marker, this method has been shown to be an easy, fast and reliable alternative to the more traditional methods for the determination of MYCN amplification and neuropeptide Y gene expression. The combination with single cell picking in the neuroblastoma tissue may be a future target of the application of real-time PCR.

Biomarkers, Tumor↗

PubMed2000

Gene expression of neuronal nitric oxide synthase and adrenomedullin in human neuroblastoma using real-time PCR.

The objective of our study was to assess the gene expression of the antiproliferative systems neuronal nitric oxide synthase (nNOS) and adrenomedullin (AM) in human neuroblastoma. A novel real-time PCR method was evaluated using neuropeptide Y (NPY) for validation. Glyceraldehyd-3-phospate dehydrogenase (GAPDH) and NPY gene expression in neuroblastomas of 50 patients were measured in parallel by competitive quantitative and TaqMan real-time RT-PCR. AM and nNOS mRNA were determined by real-time PCR. Our results showed a linear relationship between competitive quantitative and real-time RT-PCR measurements of NPY and GAPDH (r = 0.87 and r = 0.92, respectively). AM and nNOS mRNA was found in all tumor samples. AM/GAPDH mRNA increased with higher differentiation according to Shimada (p = 0.013). There was no relation between MYCN amplification nor with the tumor stage (p = 0.78 and p = 0.30, respectively). AM/GAPDH did not relate to recurrence or death in a 5-year follow-up period. Neuronal NOS/GAPDH expression did not relate to any biological or clinical parameter of prognosis or differentiation. Similar results were obtained when the neuronal marker protein gene product 9.5 (PGP9.5) was used to normalize mRNA concentration. In conclusion, TaqMan real-time PCR appears to be a reliable method to quantify gene expression in neuroblastomas. Adrenomedullin mRNA in neuroblastoma is linked to tumor differentiation but not to prognostic markers.

Adolescent↗

PubMed2000

Recovery from withdrawal of inhaled nitric oxide and kinetics of nitric oxide-induced inhibition of nitric oxide synthase activity in vitro.

OBJECTIVE: To examine the kinetics of successful nitric oxide (NO) withdrawal in vivo and in vitro. DESIGN AND SETTING: Prospective study in a university pediatric intensive care ward and research laboratory. PATIENTS AND MATERIALS: Nineteen patients with acute respiratory distress syndrome (ARDS) or persistent pulmonary hypertension of the newborn (PPHN). Primary porcine pulmonary artery cells in vitro. INTERVENTIONS: NO inhalation and withdrawal in patients; exposure to NO donor sodium nitroprusside (SNP) and gaseous NO in vitro. MEASUREMENTS AND RESULTS: In patients: a slight, but significant, increase of oxygenation index (OI) from 4.57 +/- 0.24 cmH2O/torr (mean +/- SEM) to 4.90 +/- 0.26 cmH2O/torr after withdrawal of NO (p < 0.001). Recovery of OI (4.43 +/- 0.23 cmH2O/torr) 30 min after weaning, a significant drop after 4 h (3.72 +/- 0.17 cmH2O/ torr;p < 0.001), values restored after 12 h. In vitro: NO synthase (NOS) activity was significantly lower in SNP-incubated cells (20.0 +/- 4.0 microM/min) than in control cells (37.6 +/- 7.0 microM/ min; p < 0.05). Thirty minutes after SNP withdrawal there was NOS activity of 35.8 +/- 10.0 microM/min with a significant increase by 4 h (p < 0.05). No alteration of endothelial NOS (ENOS) mRNA expression by NO (Northern Blot). CONCLUSION: In patients there is a slight, but significant, reversible increase of OI after successful weaning from NO. In vitro, NO leads to a reversible decrease of ENOS activity on a post mRNA level, resembling clinical observations.

Administration, Inhalation↗

PubMed2000

Comparison of methylene blue, riboflavin, and N-acetylcysteine for the reduction of nitric oxide-induced methemoglobinemia.

OBJECTIVE: To investigate the treatment of nitric oxide (NO)-induced methemoglobinemia by methylene blue (MB), riboflavin, and N-acetylcysteine (NAC) in vitro. DESIGN: Prospective, controlled in vitro study. SETTING: Research laboratory in a university hospital. PARTICIPANTS: Five healthy volunteers. INTERVENTIONS: Generation of 16% to 18% of methemoglobin in red blood cells by NO and subsequent addition of MB, riboflavin, or NAC. Simultaneous NO (32 ppm) and MB or riboflavin exposure of red blood cells. Induction of 14% to 18% of methemoglobin in red blood cells by NO, subsequent addition of MB or riboflavin, and further incubation with NO (80 ppm). MEASUREMENTS AND MAIN RESULTS: After discontinuation of NO, mean half-life for methemoglobin was significantly reduced by MB from 356 mins (controls) to 5 mins (10 microM) in a dose-dependent manner (p < .001). NAC did not alter the half-life for methemoglobin, and a reduction from 356 to 168 mins was seen for 120 microM riboflavin (p < .001). Methemoglobin formation after 3 hrs of NO exposure was 4.3%+/-0.7% in controls and 0.3%+/-0.1% with 10 microM MB (p < .001); 1 microM MB attenuated methemoglobin formation to 1.9%+/-0.1% (p < .01). With riboflavin (120 microM), methemoglobin was 2.2%+/-0.5% vs. 3.2%+/-0.6% in controls (p < .001). In the presence of high methemoglobin concentrations, further methemoglobin formation was inhibited by 1 and 10 microM MB (p < .001) and attenuated by 0.1 microM MB (p < .001) but not by riboflavin. CONCLUSIONS: In vitro, NO-induced methemoglobin formation is significantly decreased by medium (1 microM) and high (10 microM) concentrations of MB and partially by high riboflavin concentrations (120 microM). NAC and low concentrations of riboflavin do not alter methemoglobin formation.

Acetylcysteine↗

PubMed2000

Case of XXXXY syndrome. Development throughout adolescence and endocrine aspects.

49,XXXXY syndrome is a very rare condition that is associated with a considerable more severe phenotype than classic 47,XXY Klinefelter syndrome. We present a patient with 49,XXXXY syndrome, who was first presented to an endocrinological unit at the age of 12.5 years with prepubertal genitalia. He was then lost from follow-up and showed clear clinical and biochemical signs of hypergonadotropic hypogonadism when presenting again at the age of 16 years. The patient was started on testosterone replacement therapy. This case is reported to underline the need for thorough endocrinological follow-up examinations in males with X polysomies.

Adolescent↗

PubMed2000

Variability of leptin values measured from different sample matrices.

Leptin concentrations are usually determined in serum or EDTA-treated plasma. Our aim was to evaluate the precision and accuracy of leptin measurement from serum and various kinds of plasma. Blood samples were collected from healthy volunteers and divided into aliquots of serum and plasma with administration of K(2)-EDTA, citrate, fluoride and lithium-heparinate, respectively. Leptin concentrations were measured by a specific radioimmunoassay. There were clear differences between the leptin values from the different matrices. The coefficient of variation (CV) was highest in serum samples (CV: 11.9 %) and very low in K(2)-EDTA-treated plasma samples (CV: 5.3%). Leptin measurements from serum yielded significantly lower results than the respective K(2)-EDTA-treated plasma samples (p < 0.05). The measurement in Li-heparinate-treated plasma revealed similar results to that in K(2)-EDTA-treated plasma. The lowest CV was determined in fluoride-treated plasma (5.2%). A higher CV was determined in citrate-treated plasma (5.8%) and the values were about 25% lower than in the respective K(2)-EDTA-treated plasma samples (p < 0.0001). Lower leptin measurements in citrate-treated plasma may partially, but not in total, be a consequence of dilution by anticoagulating additives. Because of the low CV K(2)-EDTA- and Li-heparinate-treated plasma samples appear most reliable for the measurement of leptin. The usage of these sample matrices is therefore recommended.

Adult↗

PubMed2000

Evidence for change of 11beta-hydroxysteroid dehydrogenase activity during infancy and childhood.

The conversion of cortisol (F) to cortisone (E) is catalyzed by 11beta-hydroxysteroid dehydrogenase type 2. The present study was designed to investigate the changes of F and E plasma concentration as an indirect measurement of 11beta-hydroxysteroid dehydrogenase activity in infancy and childhood. Plasma samples were obtained from 262 healthy children and adolescents aged 1 d to 18 y. Plasma F and E were measured, using specific radioimmunoassays after extraction and automated Sephadex LH 20 chromatography. The F/E ratio was calculated to assess 11beta-hydroxysteroid dehydrogenase activity. During the first year of life, plasma F levels rose significantly (r(2) = 0,24; p = 0.01), and thereafter no further increase was seen until adulthood (r(2) = 0.01; p = 0.86). In contrast, plasma E significantly decreased during the first year of life (r(2) = -0.35; p<0.001) and stayed unchanged thereafter (r(2) = 0.02; p = 0.81). As a consequence, the F/E ratio rose significantly during the first year (r(2) = 0.67; p<0.001) but did not change afterward (r(2) = 0.001; p = 0.99). During the first year of life, there is a change from the predominance of E, with low mineralocorticoid receptor affinity, to F, with high mineralocorticoid receptor affinity. This shift corresponds to the declining plasma concentrations of aldosterone during infancy. The changes may indicate a not yet recognized, significant change of 11beta-hydroxysteroid dehydrogenase isoenzyme activity or alterations in the secretion of F and E, which may be of relevance for the development of arterial blood pressure in infancy.

11-beta-Hydroxysteroid Dehydrogenases↗