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Biomedical subjects

S Pedersen

Publications and source records attributed to S Pedersen.

At least 55 records · Page 3Linked to original sources
PubMed1999

Short-term lower leg growth rate in children with rhinitis treated with intranasal mometasone furoate and budesonide.

BACKGROUND: Mometasone furoate (MF) aqueous nasal spray is a potent intranasal glucocorticoid with low systemic bioavailability. Knemometry has been shown to be a sensitive method of detecting systemic effects of exogenous steroids in children. OBJECTIVE: We sought to assess whether MF (100 or 200 microg) or budesonide intranasal aqueous spray (400 microg) influences the short-term lower leg growth rate in children with seasonal or perennial allergic rhinitis. METHODS: MF, budesonide, and placebo were administered once daily for 2 weeks to 22 children aged 7 to 12 years (mean, 10 years) in a randomized, double-blind, crossover study. Lower leg measurements were done before and after each 2-week treatment period. Two-week washout intervals separated each treatment period. RESULTS: There were no significant differences in lower leg growth rates among the MF 200 microg (0.95 +/- 0.79 mm; mean +/- SD), budesonide 400 microg (0.73 +/- 0.61 mm), or placebo (0.69 +/- 0.70 mm) groups. The growth rate of the group receiving a 100-microg dose of MF (1.16 +/- 0.67 mm) was greater than that for the group receiving placebo (P =.024) or budesonide (P =.033). No statistically significant sequence effect (P =.11), carry-over effect (P =.24), overall treatment effect (P =.086), or period effect (P =.065) was detected. CONCLUSION: No short-term adverse effects on linear lower leg growth rates were detected after once daily MF or budesonide at clinically relevant doses.

Administration, Intranasal↗
PubMed1999

Drug delivery from the Turbuhaler and Nebuhaler pressurized metered dose inhaler to various age groups of children with asthma.

A total of 198 children aged 3 to 15 years inhaled a single dose of 200 micrograms budesonide from a Nebuhaler pressurized metered dose inhaler (pMDI) and a Turbuhaler dry powder inhaler in a randomized crossover study. The budesonide dose delivered to a patient was assessed by measuring the amount of drug deposited on a filter inserted between the inhaler outlet and the patient's mouth. The dose of budesonide deposited on the filter and the estimated dose of particles with a mass median aerodynamic diameter (MMAD) of 5 microns or less after inhalation from the Turbuhaler were both approximately twice the values inhaled from the pMDI Nebuhaler in children less than 5 years of age (P < 0.01). The variation in the dose delivered to the patient was similar for the two inhalers in children over 5 years old. In 3- to 4-year-old children, dose delivery to the patient was higher and/or more consistent from the pMDI Nebuhaler than from the Turbuhaler. Filter dose after Turbuhaler treatment varied significantly from peak inspiratory flow rate through the Turbuhaler (PIFTbh) (P < 0.01). The percentage of children producing a PIFTbh greater than 50 L/min decreased with age (89%, 45%, and 14% in 5-, 4-, and 3-year-old children, respectively). It is concluded that drug delivery to a child with asthma varies with age and inhalation device. Further studies are needed to assess the clinical importance of this finding.

Administration, Inhalation↗
PubMed1999

Systemic availability and pharmacokinetics of nebulised budesonide in preschool children.

AIM: To evaluate the systemic availability and basic pharmacokinetic parameters of budesonide after nebulisation and intravenous administration in preschool children with chronic asthma. METHODS: Plasma concentrations of budesonide were measured for three hours after an intravenous infusion of 125 micrograms budesonide. The children then inhaled a nominal dose of 1 mg budesonide through the mouthpiece of a Pari LC Jet Plus nebuliser connected to a Pari Master compressor, and the plasma concentrations of budesonide were measured for another six hours. The amount of budesonide inhaled by the patient ("dose to subject") was determined by subtracting from the amount of budesonide put into the nebuliser, the amount remaining in the nebuliser after nebulisation, the amount emitted to the ambient air (filter), and the amount found in the mouth rinsing water. RESULTS: Ten patients aged 3 to 6 years completed both the intravenous and the inhaled treatment. The mean dose to subject was 23% of the nominal dose. The systemic availability of budesonide was estimated to be 6.1% of the nominal dose (95% confidence intervals (CI), 4.6% to 8.1%) or 26.3% of the dose to subject (95% CI, 20.3% to 34.1%). Budesonide clearance was 0.54 l/min (95% CI, 0.46 to 0.62), steady state volume of distribution 55 litres (95% CI, 45 to 68), and the terminal half life was 2.3 hours (95% CI, 2.0 to 2.6). CONCLUSIONS: Approximately 6% of the nominal dose (26% of the dose to subject) reached the systemic circulation of young children after inhalation of nebulised budesonide. This is about half the systemic availability found in healthy adults using the same nebuliser.

Anti-Inflammatory Agents↗
PubMed1998

The modification of the wobble base of tRNAGlu modulates the translation rate of glutamic acid codons in vivo.

In Escherichia coli, uridine in the wobble position of tRNAGlu and tRNALys is modified to mnm5s2U34. This modification is believed to restrict the base-pairing capability, i.e. to prevent misreading of near-cognate codons and reduce the efficiency of cognate codon reading, especially of codons ending in G. We have determined the influence of the 5-methylaminomethyl and the 2-thio modifications of mnm5s2U34 in tRNAGlu on the translation rate of the glutamate codons GAA and GAG in vivo. In wild-type cells, GAG is translated slower (7. 7 codons/second) and GAA faster (18 codons/second) than the average codon (13 codons/second). Surprisingly, tRNAGlu lacking the 5-methylaminomethyl group, thus containing s2U34, translated GAA twofold faster (47 codons/second) and GAG fourfold slower (1.9 codons/second) than fully modified tRNAGlu. In contrast, tRNAGlu that contains mnm5U34 instead of mnm5s2U34 translated GAA fourfold slower (4.5 codons/second) and GAG only 20% slower (6.2 codons/second). Clearly, the 5-methylaminomethyl group of mnm5s2U34 facilitates base-pairing with G while decreasing base-pairing with A, resulting in rates of translation of GAG and GAA that approach that of the average codon. The 2-thio group increases the recognition of GAA and has only a minor effect on the decoding of GAG. Furthermore, the 2-thio group is important for aminoacylation (see the accompanying paper). These data imply that the function of mnm5s2U34 may be different from what has been suggested previously.

Codon↗
PubMed1998

P2 receptor-mediated signal transduction in Ehrlich ascites tumor cells.

The mechanisms, by which the P2 receptor agonists adenosine 5'-triphosphate (ATP) and uridine 5'-triphosphate (UTP) evoke an increase in the free cytosolic calcium concentration ([Ca2+]i) and in intracellular pH (pHi), have been investigated in Ehrlich ascites tumor cells. The increase in [Ca2+]i evoked by ATP or UTP is abolished after depletion of intracellular Ca2+ stores with thapsigargin in Ca2+-free medium, and is inhibited by U73122, an inhibitor of phospholipase C (PLC), indicating that the increase in [Ca2+]i is primarily due to release from intracellular, Ins(1,4,5)P3-sensitive Ca2+ stores. ATP also activates a capacitative Ca2+-entry pathway. ATP as well as UTP evokes a biphasic change in pHi, consisting of an initial acidification followed by alkalinization. Suramin and 4,4'-diisothiocyano-2,2'-stilbene-disulfonic acid (DIDS) inhibit the biphasic change in pHi, apparently by acting as antagonists at P2 receptors. The alkalinization evoked by the P2 receptor agonists is found to be due to activation of a 5'-(N-ethyl-N-isopropyl)amiloride (EIPA)-sensitive Na+/H+ exchanger. ATP and UTP elicit rapid cell shrinkage, presumably due to activation of Ca2+ sensitive K+ and Cl- efflux pathways. Preventing cell shrinkage, either by incubating the cells at high extracellular K+ concentration, or by adding the K+-channel blocker, charybdotoxin, does not affect the increase in [Ca2+]i, but abolishes the activation of the Na+/H+ exchanger, indicating that activation of the Na+/H+ exchanger is secondary to the Ca2+-induced cell shrinkage.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1998

Ribosomal protein S1 is required for translation of most, if not all, natural mRNAs in Escherichia coli in vivo.

We have deleted the chromosomal rpsA gene, encoding ribosomal protein S1, from an Escherichia coli strain carrying a plasmid where rpsA was controlled by the lac promoter and operator. This exogenous source of protein S1 was essential for growth. Thus we have verified the absolute requirement for protein S1. To see if translation of individual mRNAs differed in the requirements for protein S1, we removed the inducer and followed the time-course of the synthesis of several individual proteins and of total RNA, DNA and protein. Growth immediately shifted from being exponential to being linear, with a rate of protein synthesis defined by the pre-existing amount of protein S1. The expression pattern of the individual proteins indicated that the translation of all mRNAs was dependent on protein S1. Unexpectedly, we found that depletion for protein S1 for extended periods introduced a starvation for amino acids. Such starvation was indicated by an increased synthesis of ppGpp and could be reversed by addition of a mixture of all 20 amino acids. Measurements of the peptide chain elongation rate in vivo showed that ribosomes without protein S1 were unable to interfere with the peptide chain elongation rate of the active ribosomes and that, therefore, protein S1 was unable to diffuse from one ribosome to another during translation. We conclude that protein S1-deficient ribosomes are totally inactive in peptide chain elongation on most, if not all, naturally occurring E. coli mRNAs.

Bacterial Proteins↗
PubMed1998

Swelling-activated potassium currents of Ehrlich ascites tumour cells.

The K+ and Cl- currents activated by Ca2+-ionophore treatment or by hypotonic cell swelling have been studied in Ehrlich ascites tumour cells by the patch-clamp technique. A charybdotoxin-inhibitable K+ current was activated by increasing intracellular Ca2+ concentration. In contrast, the K+ current activated by cell swelling was insensitive to charybdotoxin as well as to apamin, suggesting that channels different from those sensitive to Ca2+ are responsible for regulatory volume adjustments in these cells. The magnitude of the K+ and Cl- currents activated by hypotonic challenge was markedly temperature-dependent, possibly reflecting the temperature-dependence of enzymes involved in the intracellular signalling of cell volume regulation.

Animals↗
PubMed1998

Effect of salmeterol treatment on nitric oxide level in exhaled air and dose-response to terbutaline in children with mild asthma.

The aim of this study was to investigate whether regular treatment with inhaled salmeterol modifies the dose-response curve to the inhaled short-acting beta2-agonist terbutaline or affects the concentration of nitric oxide (NO) in exhaled air of children with asthma. Twenty-two children aged 7 to 15 years (mean = 11.6 years) with mild asthma were treated with inhaled 50 microg salmeterol twice daily or placebo for 3 weeks in a randomized double-blind cross-over study. These treatments were followed by treatment with inhaled 200 microg budesonide twice daily for 3 weeks. On the last day of each period, NO level was measured in exhaled air and a cumulative dose-response experiment with terbutaline (cumulative dose: 1,475 microg) was performed. Baseline lung functions after salmeterol treatment were significantly higher than baseline after placebo (P + 0.05). Salmeterol treatment flattened out the dose-response curve to terbutaline such that higher doses of terbutaline were required to produce the same degree of bronchodilation (ED50 for FEV1 was increased by an estimated factor of 70 (95% CI: 0.8-6307) and ED50 for FEF25-75 by a factor of 41 (95% CI: 6.7-254); P < 0.05). NO levels were unaffected by salmeterol treatment (12.7 ppb; placebo = 10.7 ppb), but were significantly reduced during budesonide therapy (5.2 ppb; P < 0.001). The corresponding maximal NO levels were 19.5 (placebo), 22.9 (salmeterol), and 9.4 ppb (budesonide). We conclude that 3 weeks treatment with salmeterol does not affect NO levels in exhaled air, but it significantly changes the dose-response curve to terbutaline.

Adolescent↗
PubMed1998

Measuring efficacy and safety of different inhaled corticosteroid preparations.

Inhaled corticosteroids are the mainstay of treatment for persistent asthma because of their proven efficacy, which is better than any other class of antiasthma therapy. Concerns about unwanted systemic effects with long-term use has, however, limited their use. Efforts have been made to develop inhaled corticosteroids with less systemic activity for a given clinical effect, thereby improving their therapeutic index. Many different study designs and outcome variables have been used to compare different inhaled corticosteroids. Differences in pharmacologic properties between drugs are most easily and accurately measured and quantified by measures of systemic effects. However, these differences should always be related to differences in clinical effects. It is difficult to draw firm conclusions with respect to the therapeutic index of different inhaled corticosteroids because no direct placebo-controlled, dose-response comparisons of clinical effects have been made. Despite this caveat, the available studies suggest that microgram for microgram, when delivered by a pressurized metered-dose inhaler (pMDI), fluticasone propionate (FP) is more effective than beclomethasone dipropionate (BDP), triamcinolone acetonide (TAA), or budesonide; however, the efficacy of budesonide delivered by Turbuhaler is equipotent to that of FP delivered by pMDI or Diskhaler and more effective than that of BDP. When comparative safety is considered, budesonide or TAA delivered by pMDI have less systemic activity than FP delivered by pMDI, whereas BDP and FP delivered by pMDI appear to be equivalent. Also, budesonide delivered by Turbuhaler has less systemic activity than FP delivered by Diskhaler.

Administration, Inhalation↗
PubMed1998

Importance of training for correct Turbuhaler use in preschool children.

AIM: To study the impact of both audiovisual information and nurse-training on the use of budesonide Turbuhaler in preschool children who had never used a dry powder inhaler. DESIGN: A single-blind, randomized, parallel-group trial studied 72 children aged 3-5 y. All children and their parents were shown an instructional video and given written instruction. After this, peak inspiratory flow (PIF1) through Turbuhaler was measured. Children in group A (n = 36) then received individual training by a nurse while those in Group B (n = 36) did not and PIF2 was measured. Afterwards, Group B received similar individual training while Group A received no additional training, and PIF3 was measured. Group A was given a placebo Turbuhaler and encouraged to practice at home. Two weeks later, both groups returned to the clinic where PIF4 was measured. RESULTS: The number of children who were able to correctly perform PIF1, PIF2 and PIF4 in Group A was 27, 34 and 36, respectively. The corresponding numbers for Group B were 30, 29, and 29. No effect of training was seen in 3-y-old children. Individual training by a nurse was associated with a statistically significant increase in PIF2 (10 l/min; p = 0.014). Moreover, 2 weeks of home training was associated with an additional increase in PIF of 8 l/min compared with Group B (p < 0.015). After individual instruction and home training, mean PIF in children aged 4 and 5 was 56 (42-72) and 55 (41-66) l/min, respectively. CONCLUSION: After individual instruction and training at home, the vast majority of children aged 4 and 5 y can use Turbuhaler correctly. Audiovisual information and individual instruction is not sufficient in the majority of these children. Few 3-y-old children can learn the correct use of Turbuhaler.

Analysis of Variance↗
PubMed1998

Bone mineral density in children with asthma receiving long-term treatment with inhaled budesonide.

The aim of our study was to assess the effects of long-term treatment with inhaled budesonide (BUD) on total body bone mineral density (BMD), total body bone mineral capacity (BMC), total bone calcium (TBC), and body composition in children with asthma. Dual energy X-ray absorptiometry (DEXA scan) was performed in 157 asthmatic children treated with inhaled BUD at a mean daily dose of 504 microg (range, 189 to 1,322 microg) for 3 to 6 yr (mean, 4.5 yr). Measurements were compared with those of 111 age-matched children also suffering from asthma but who had never been treated with exogenous corticosteroids for more than 14 d (control group). There were no statistically significant differences between the two groups in BMD (BUD = 0.915 g/cm2, controls = 0.917 g/cm2), BMC (BUD = 1,378 g, controls = 1,367 g), TBC (BUD = 524 g, controls = 519 g), or body composition (lean body weight = 27,600 g [BUD] and 26,923 g [control], % body fat = 20.1% [BUD] and 20.3% [control]). Furthermore, there was no correlation between any of these parameters and duration of treatment, accumulated or current dose of budesonide. Three to six years of treatment with inhaled budesonide at an average daily dose of 504 microg has no adverse effect on total BMD, total BMC, TBC, or body composition in children with chronic asthma.

Absorptiometry, Photon↗
PubMed1998

Posterior subcapsular cataracts, bruises and hoarseness in children with asthma receiving long-term treatment with inhaled budesonide.

We assessed the effect of long-term treatment with inhaled budesonide (BUD) on the occurrence of posterior subcapsular cataracts (PSC), bruises and hoarseness in children with asthma. Slit lamp examinations were performed in 157 asthmatic children treated with inhaled BUD at a mean daily dose of 504 microg (range 189-1,322 microg) for 3-6 yrs (mean 4.4 yrs). Measurements were compared with 111 age-matched children with asthma, who had never received treatment of exogenous corticosteroids (control group). The children were examined for bruises, their tendency to bruise and occurrence of voice changes. No incidents of PSC ascribable to BUD treatment were seen. One patient in the BUD group had been diagnosed with PSC before the study and this was still present. There were no statistically significant differences in number of bruises between the two groups (BUD=33, controls=3.2; p=0.70), area covered by bruises (BUD=10 cm2, controls=10.1 cm2; p=0.97), tendency to bruise (BUD=5/10, controls=5/10) or occurrence of hoarseness (BUD=20%, controls=21%; p=0.92). Furthermore, there was no correlation between the occurrence of bruises or tendency to bruise and duration of treatment, accumulated or current dose of BUD. A 3-6 yr treatment of children with inhaled budesonide at an average daily dose of about 500 microg is not associated with an increased occurrence of posterior subcapsular cataract, bruises, tendency to bruise, hoarseness or other noticeable voice changes.

Administration, Inhalation↗
PubMed1998

[Dust reduction in pig houses].

Airborne dust in pig houses causes health problems for humans with full-time employment in pig houses. Many attempts have been made to reduce the dust burdens, but often without sufficient results. At Research Centre Bygholm ten different possibilities for dust reduction have been tested in the test section, and the results are evaluated on the basis of results obtained simultaneously in an identical control section. Until now, the two most efficient methods are addition of fat to the pigs' diet and spraying a thin layer of rape seed oil in the animal house. By adding 4% of fat to the diet, a reduction of 50% can be seen, and by spraying 5 g of rape seed oil daily per pig place, the aerial dust concentration can be reduced to about 75%. The costs are about 1 DM/pig at a price of rape seed oil of 2 DM/l.

Animal Husbandry↗