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Biomedical subjects

Alicja Grzanka

Publications and source records attributed to Alicja Grzanka.

7 recordsLinked to original sources
PubMed2004

[Beta2-agonists--what does their chemical structure determine?].

The paper presents the structure and functional relationship of beta2-agonists and the beta2-adrenoceptor. The human beta2-adrenoceptor is a member of the 7-transmembrane family of receptors. Most of the actions of the beta2-receptor are mediated through the Gs protein and the cAMP-dependent PKA system. Alternative cAMP-independent pathways affected following beta2-receptor activation have also been described. Beta2-agonists have been used as bronchodilator agents in the treatment of asthma since the development of inhaled isoprenaline preparations in 1961. Over the years, these agents have been markedly improved through the development of short-acting beta2 selective agents followed by long-acting beta2 selective agents with prolonged duration of action. Efforts directed towards improving the pharmacodynamic and pharmacokinetic properties, including the long-acting and selective beta2-adrenoceptor agonists, included two major pathways of modifying the basic structure of the catecholamines, which are described in this paper. The pharmacological activity usually resides in the (R)-enantiomer. The kinetics of beta2-agonist-stimulated bronchodilation in asthma is determined by the differences in the molecular mechanism of beta2-agonists action. Regulation of the beta2-receptor is influenced by its desensitization following exposure to high concentrations of or repeated challenges with agonists, and up-regulation which can be induced by glucocorticoids and thyroid hormones.

Adrenergic beta-Agonists↗
PubMed2004

[Lung function and exercise tolerance after treatment with salmeterol or ipratropium bromide in chronic obstructive pulmonary disease].

The aim of this study was to compare the effects of 6 months therapy with salmeterol or ipratropium bromide on lung function (resting and dynamic parameters), exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). In open, randomised study patients at visit 1 were included into trial, at visit 2 and, after 6 months therapy, at visit 3 lung function measured by a pressure body plethysmography, exercise tolerance was investigated by 6 minute walking test and dyspnoea was analysed by the means of Borg scale. We studied 24 patients (18 males, 6 females, range age 45-76 yrs, mean: 60.2+/-10.46) with stable COPD. 13 subjects (mean FEV1 = 63.61% predicted, SD = 15.66%) received salmeterol (2 x 50 microg/day) and 11 subjects (mean FEV1 = 62.52% predicted, SD = 12.39%) received ipratropium bromide (4 x 40 microg/day). There were no significant changes in lung function parameters (FEV1, VC, Rtot, TLC, RV and RV%TLC) after 6 months therapy with both drugs, but the treatment with salmeterol significantly improves exercise tolerance in 6 minute walking test (p=0.048) and Borg dyspnea ratings (p=0.008).

Aged↗
PubMed2004

[Assessment of antioxidative enzymes activity and intensification of lipids peroxidation in asthmatic patients].

Chronic immunoallergic inflammatory reaction plays a key role in pathogenesis of asthma. Importance of free oxygen radicals in mechanism of chronic inflammatory process has been proved. Activity of two antioxidative enzymes: isoenzymes of superoxide dismutase (SOD), glutathione peroxidase (POX), and concentration of malondialdehyde (MDA) in serum and erythrocytes in asthmatics during exacerbation and improvement of disease were assessed. Disturbances in oxidative system in asthmatic patients have been observed. Lack of significant differences in antioxidative indexes between a period of exacerbation, not complicated by infection and a period of improvement indicates a pathophysiological role of chronic oxygen stress in asthma. It has been also shown that bacterial infection disturbs efficiency of antioxidative mechanisms.

Acute Disease↗
PubMed2003

[Polymorphism of beta 2-adrenergic receptors].

The human beta 2-adrenoceptor is a member of the seven-transmembrane family of receptors. It is expressed in many cell types such as airway smooth muscle cells, neutrophils, eosinophiles, alveolar macrophages and airway epithelial cells. The beta 2-adrenoceptor agonists are the most important group of bronchodilator drugs used in the treatment of asthma. They are classified by their selectivity, affinity for the receptor, potency and pharmacological efficacy. The gene encoding the beta 2-adrenergic receptor is highly polymorphic in the human population. Polymorphism affecting amino acids 16, 27 and 164 are the most common and they have been shown to correlate with some clinical features of asthma, including airways reactivity. They can modulate the behaviour of the beta 2-receptor, altering ligand binding and the characteristics of down-regulation following agonist exposure. The homozygous glycine-16 (Arg-->Gly) variant of the beta 2-adrenoceptor is known to predispose to agonist-induced down-regulation and desensitization, and may play a role in the pathogenesis of asthma severity. The polymorphism at position 27 (Gln-->Glu) is associated with decreased airway responsiveness. The polymorphic variant 164 (Thr-->Ile) shows impaired agonist binding and decreased adenylyl cyclase activity. No convincing evidence has been presented demonstrating a linking of asthma per se with this receptor polymorphism.

Adrenergic beta-Agonists↗
PubMed2003

The effect of short-term and chronic glucocorticoid therapy on lymphocyte glucocorticoid receptor number in patients with asthma.

Glucocorticoid (GCs) hormones are widely used in the treatment of bronchial asthma. However, not all aspects of their pharmacological effects are well understood as yet. It is know that the effects of GCs are mediated through GC receptors (GCRs). We sought to evaluate the effect of short-term and chronic GC therapy on GCR number in peripheral blood lymphocytes, the relationship between GCR number and cortisol concentrations in asthma patients treated with GCs as well as the response to GC therapy in various pictures of this disease. Sixty-nine patients with bronchial asthma were investigated. Thirty-five of them had received steroid therapy: 18 patients for 1 to 15 years and 17 patients for 13 days after a prior 3-month discontinuation of steroid treatment. The control group consisted of 28 healthy, age-matched volunteers. GCR numbers were determined using tritriated dexamethasone as a ligand. The scatchard method was applied to calculate the maximal specific binding and the dissociation constant. The number of receptor sites per lymphocyte was calculated. Cortisol was measured by radioimmunoassay. Lymphocyte GCR numbers in patients with bronchial asthma who were not treated with steroids, did not differ from age-matched healthy persons (means 8115+/-812 and 7905+/-832). A significant decrease in receptor number was seen in patients receiving steroid therapy (mean 4331+/-1041). There was also a significant difference in receptor number between the groups with short-course (mean 3741+/-549) and chronic steroid therapy (mean 4885+/-1095). The number of GCRs did not correlate with age, sex, clinical state or serum cortisol concentration in either group.

Adolescent↗