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  • 11
    ISSN: 1432-1076
    Keywords: β-Adrenoceptor density ; β-Adrenoceptor affinity ; High and low receptor affinity state ; B and T-cells ; Asthmatic children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract β-adrenoceptor binding in lymphocytes of asthmatic and non-asthmatic children and healthy adult volunteers was investigated with the radioligand 125-iodocyanopindolol (ICYP). Binding studies were performed with 4 to 5 different concentrations of ICYP. Receptor density and affinity were calculated by Scatchard plots. Resolution of β-adrenoceptors into those of high and low affinity state was obtained from inhibition curves with salbutamol using Hofstee plots. Receptor density in B-cell enriched fractions was two to three-fold higher than in T-cells for all patients and volunteers studied (P less than 0.025). No difference in β-adrenoceptor density on B and T-cells occurred neither in age-matched asthmatic and non-asthmatic children nor in adult volunteers. The affinity of β-adrenoceptors did not differ for B and T-cells nor for the patients or volunteers studied. However, when two distinct binding states for β-adrenoceptor agonists were obtained using salbutamol displacement curves it appeared that β-adrenoceptors on T-cells were at a higher affinity state compared to those on B-cells in asthmatic and non-asthmatic children, as well as in adults. Since the ability of an agonist to activate adenylate cyclase correlates closely with the amount of high affinity receptor state formed in the presence of the agonist, increased intrinsic activity of the β-adrenoceptor agonist on T-cells may be postulated. In conclusion, age-related control groups and determination of the B/T ratio are neccessary for interpretation of β-adrenoceptor changes in bronchial asthma.
    Type of Medium: Electronic Resource
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  • 12
    ISSN: 1432-1076
    Keywords: Human basophils ; Histamine release ; Pertussis toxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of childhood pertussis infection and of purified pertussis toxin on histamine relase from human basophil leucocytes was investigated. Three different stimuli, the peptide N-formyl-Met-Phe (NFMP), anti-IgE, and the calciuminnophore A23187 were used to challenge the cells. When NFMP was the stimulus, histamine release in the control group (age 0.5–17 years) increased in an age-dependent fashion, whereas anti-IgE and A23187 stimulated release did not vary with age. During the convulsive state of pertussis infection there was a significant reduction of histamine release in response to 10 μM NFMP (from 9.5±1.4 [n=21] to 6.7±1.5 [n=19],P〈0.05) and in response to 800 and 80 U/ml anti-IgE (from 28.5±5 [n=19] to 16.3±5 [n=13],P〈0.05, and from 6.9±1.7 [n=16] to 2±0.8 [n=13],P〈0.01), whereas histamine release stimulated by A23187 was unchanged compared to release in control children. In vitro pretreatment of basophils from healthy children and adults with pertussis toxin also inhibited histamine release. When NFMP was the stimulus, release was completely blocked by pertussis toxin with an IC50 of about 11 ng/ml whereas anti-IgE stimulated release was only inhibited by 20%–30% and release induced by A23187 was reduced to 40%–50% by toxin treatment. In conclusion we have demonstrated a functional impairment of histamine release during the convulsive state of pertussis and that this inhibition is likely to be mediated by pertussis toxin.
    Type of Medium: Electronic Resource
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 134 (1980), S. 45-50 
    ISSN: 1432-1076
    Keywords: Exercise induced asthma (EIA) ; Catecholamines ; Cyclic AMP ; a-Adrenergic blockade ; Allergic asthma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to provoke exercise induced asthma (EIA) a test which involved running for 7 min was performed with 21 asthmatic children. Eleven children not only developed a highly significant increase in airway resistance (Rt), but showed also a 4-fold increase in plasma noradrenaline (NA) levels. In 10 children who did not develop EIA only a 1.5-fold increase of NA could be observed. Following exercise cyclic AMP showed an identical increase in both groups studied, whereas adrenaline levels remained uninfluenced. Tests carried out after administration of phentolamine by inhalation showed a significant inhibition of post-exercise bronchoconstriction. It is concluded that EIA originates from a-receptor stimulation which is mediated by excessive noradrenaline release. However, since disodium cromoglycate—which does not act via adrenergic mechanisms—also protected against EIA, other factors should be involved. In 5 children with allergic asthma, asthmatic attacks were accompanied by a significant decrease in cAMP, whereas noradrenaline levels remained uninfluenced. Thus, evidence appears that both types of asthma result from different autonomic dysfunctions.
    Type of Medium: Electronic Resource
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 138 (1982), S. 285-285 
    ISSN: 1432-1076
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 15
    ISSN: 1432-1076
    Keywords: Calcium metabolism ; Vitamin D metabolites ; Anticonvulsant drugs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Calcium metabolism and plasma concentrations of vitamin D metabolites were investigated in 27 children on long-term anticonvulsant therapy. Serum calcium was in the low normal range, phosphorus was normal, parathyroid hormone concentrations and alkaline phosphatase were elevated. Plasma 25-hydroxyvitamin D (25-OH D) and 24,25-dihydroxyvitamin D (24,25-(OH)2D) were decreased, but 1,25-dihydroxyvitamin D (1,25-(OH)2D) was normal when compared with a synchronous control group. The serum concentrations of all anticonvulsant drugs given were measured. The decreases in 25-OH D and 24,25-(OH)2D did not depend on the blood level of a single drug, or any combination of drugs given, or on the duration of therapy. The 25-OH D levels were negatively correlated with the number of different drugs used, which may reflect the severity of the neurologic disorder, and therefore with non-specific factors such as exposure to sunlight, nutrition, or physical activity. Our data do not support the hypothesis that anticonvulsant drugs act on vitamin D metabolism.
    Type of Medium: Electronic Resource
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  • 16
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 138 (1982), S. 49-52 
    ISSN: 1432-1076
    Keywords: Kinetics ; Translactal passage ; Digoxin ; Breastfed infants
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to find out whether digoxin therapy of nursing mothers might produce discomfort in suckling infants we have investigated the kinetics of the transfer of digoxin from plasma to milk in 11 nursing mothers. After intravenous or oral application of a single dose of 0.5 mg or 0.75 mg digoxin simultaneous serum, fore- and hindmilk samples were taken. Obviously, a rapid equilibrium occurred between the serum and the milk compartments and there was no difference between fore- and hindmilk. All three digoxin concentration profiles ran parallel with a milk to serum ratio of 0.6 to 0.7. The curves could best be fitted by the sum of two exponential functions. For predicting the digoxin intake into the suckling infant, simulations were carried out on the basis of two coupled compartment models. When the kinetic milk data as well as the kinetic data obtained in infants were fitted by this model it could be shown that even in the case of long half-lives only about 3% of the therapeutic drug levels were reached in the baby. Thus, one can conclude that digoxin accumulation to toxic concentrations should not occur in infants of women treated with appropriate doses of digoxin.
    Type of Medium: Electronic Resource
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  • 17
    ISSN: 1432-1076
    Keywords: Glucocorticoid receptors ; Asthma ; Prednisolone therapy ; Free serum and urine cortisol ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The number and affinity of glucocorticoid binding sites in peripheral mononuclear cells (MNC) of asthmatic and healthy children were determined by a whole cell (3H)dexamethasone binding assay at 37°C. Using HPLC determination, corresponding serum levels of non-protein-bound (free) cortisol, whole cortisol and cortisone as well as urine excretion of free cortisone and cortisol were assessed. The average number of binding sites (BS) per cell and the dissociation constant (KD) respectively, in atopic asthmatics (7768±666 BS/MNC resp. KD=17.2±2 nM) did not differ from the values measured in our control group (8333±691 BS/MNC resp. 25.4±4.8 nM). Within the age range 1 month-15.8 years neither age-dependent changes nor sex-related differences in the number of binding sites or the KD values could be detected. Active or currently inactive asthmatics, and patients under different antiasthmatic drug regimes, had similar binding sites on MNC. No differences in serum levels of cortisol, cortisone and free cortisol or in free cortisol and free cortisone of 24-h urine samples were found between healthy children and asthmatics. After a short course of prednisolone therapy for an acute severe asthmatic attack the number of glucocorticoid binding sites in peripheral MNC decreased to an average of 4632±421 BS/MNC, whereas the dissociation constant did not change significantly (14.5±3.6 nM). The corticod-hormone pattern in the serum, 24-h urine excretion, and the normal number and affinity of glucocorticoid receptors on peripheral MNC suggest that there is no primary, general impairment of glucocorticoid metabolism in asthmatic children. Short-term glucocorticoid administration resulted in suppression of endogenous corticoids to undetectable levels accompanied by down-regulation of glucocorticoid-receptor BS to about 55% of control levels.
    Type of Medium: Electronic Resource
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  • 18
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 147 (1988), S. 121-122 
    ISSN: 1432-1076
    Keywords: α-Adrenoceptors ; β-Adrenoceptors ; Phaeochromocytoma ; Catecholamines ; Desensitization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 16-year-old boy is described who had a relapse of a phaeochromocytoma 6 years after an initially successful tumour resection. The relapse was suspected after routine testing of urinary catecholamine excretion and was confirmed by scintigraphy with 123I-meta-iodobenzylguanidine, computed tomography and magnetic resonance imaging. The plasma norepinephrine level was 3082 pg/ml (normal 〈500 pg/ml); the plasma epinephrine level was in the normal range. Surprisingly, our patient had no symptoms, including hypertension. The density of the α- and β-adrenoceptors on circulating blood cells was decreased. Postoperatively the plasma catecholamine levels were in the normal range. Three months after surgery the adrenoceptor density was almost normal. We conclude that the absence of clinical symptoms was probably due to desensitization of the adrenoceptors. After a successful operation to treat phaeochromocytoma, long-term monitoring of catecholamines is necessary to rule out an asymptomatic relapse.
    Type of Medium: Electronic Resource
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  • 19
    ISSN: 1432-1076
    Keywords: β-adrenoceptors ; Down-regulation ; Catecholamines ; Congenital heart disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Twenty-six infants and children with congenital heart disease (CHD) undergoing cardiac surgery were investigated for alterations in myocardial β-adrenoceptor density. The patients were divided into three groups according to type and severity of CHD: group I consisted of 6 patients with acyanotic shunt lesions of moderate severity; group II comprised 13 children with severe acyanotic shunt and valve lesions and group III included 7 children with cyanotic CHD. The myocardial β-adrenoceptor density was determined using (−)3-[125I] Iodocyanopindolol ([125I]ICYP) and was reduced by approximately 50% in severe acyanotic CHD (33.6 fmol/mg protein) and cyanotic CHD (35.3 fmol/mg protein) in comparison with the group with less severe acyanotic shunt defects (64.4 fmol/mg protein). The affinity dissociation constant (K d, ICYP) did not differ statistically between the groups. The proportion of β1- and β1-subpopulation was evaluated by ICI 118,551-[125I]ICYP competition studies. In group II (61.5%) and group III (69.1%) significant lower portions of β1-adrenoceptors were found compared with group I (78.2%). This shift of subpopulations was due to a decreased β1-receptor density while β2-receptor density was unchanged in all groups. While the plasma noradrenaline levels of group I were similar to those of a control group of 13 healthy children, respective values of group II and III were significantly elevated. A significant negative correlation was found between plasma noradrenaline levels and myocardial β-adrenoceptor density. It is concluded that exposure of these receptors to increased circulating catecholamines, due to an enhanced sympathetic tone, leads to a reduction of their density. Noradrenaline, a preferential agonist of β1-adrenoceptors, is most probably responsible for the shift of the β-adrenoceptor subpopulations from the β1- to β2-subtype, depending on severity and type of cardiac disease.
    Type of Medium: Electronic Resource
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  • 20
    ISSN: 1432-1076
    Keywords: Allergic asthma ; Children ; Phospholipids ; Fatty acids ; Glucocorticoids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fatty acid (FA) composition of plasma phospholipids and phospholipids extracted from peripheral mononuclear white blood cells (MNC) was investigated in 11 allergic asthmatic children (age 8.9±4.6 years), in 10 age-matched non-allergic healthy controls and in 14 allergic and non-allergic children with an acute attack of asthma, who had received prednisolone medication for 2–4 days. In allergic asthmatics eicosapentaenoic acid (20∶5n−3) was significantly elevated in both plasma and MNC. The relative amount of 20∶5n−3 in MNC as well as in plasma correlated positively with increasing levels of total serum IgE (P〈0.02). The pattern of the other FAs in plasma and of MNC phospholipids did not differ between allergic asthmatic and non-allergic control children. In children with an acute attack of asthma, who had been treated with glucocorticoids (2 mg prednisolone/kg body weight for 2–4 days), distinct changes of relative FA composition of phospholipids were restricted to plasma, where some very long chain FA (22∶4n−6, 22∶5n−6) were elevated. No significant changes in FA from MNC phospholipids could be observed after glucocorticoid treatment. These findings may indicate a possible role of 20∶5n−3, the precursor of “group 3” eicosanoids, in allergic asthmatic children.
    Type of Medium: Electronic Resource
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