Nongenomic effects of glucocorticoids

W pracy przedstawiono aktualną wiedzę dotyczącą mechanizmów działania glikokortykosteroidów (GK). Zgodnie z klasycznym modelem działania, określanym jako genomowy, GK wpływają (bezpośrednio lub pośrednio) na transkrypcję i translację genów kodujących mediatory procesu zapalnego. Aktualne badania podkreślają jednak znaczenie nietranskrypcyjnych oddziaływań GK, które ujawniają się szybko - od kilkunastu sekund do kilkunastu minut. W niegenomowym mechanizmie działania GK zasadniczą rolę odgrywają interakcje z receptorami GK zlokalizowanymi w cytoplazmie, ale przede wszystkim w błonie komórkowej, które aktywują wiele szlaków sygnałowych kinaz (MAPK, Src, PI3K) i kanałów jonowych, a także szlaki sygnałowe związane z receptorami sprzężonymi z białkiem G. Udowodniono także przekaz sygnału bez udziału receptora dla GK. Odkrycie niegenomowego mechanizmu GK pozwala lepiej zrozumieć ich przeciwzapalne i immunosupresyjne działanie.The review describes current advances in the knowledge on the mechanisms of glucocorticoid (GC) action. According to the classic genomic model, GCs bind to intracellular receptors and subsequently regulate (directly or indirectly) gene transcription and synthesis of proteins responsible for inflammatory processes. The nongenomic effects of GCs, occur rapidly within seconds or minutes of drug administration, are mediated via a cytosolic but first of all by membrane GC receptors and lead to activation of multiple signal transduction pathways of protein kinases (MAPK, Src, PI3K), cation channels or G protein- -coupled receptors. Nongenomic effects may also occur without receptor involvement. The elucidation of nongenomic actions provides new insights for the understanding of their anti-inflammatory and immunosuppressive GC effects

Nongenomic effects of glucocorticoids, an important mechanism of inhaled glucocorticoids action in asthma

W artykule przeglądowym autorzy przedstawili kliniczne implikacje niegenomowych mechanizmów działania glikokortykosteroidów, ważne także dla wziewnej drogi ich podawania. Te szybkie efekty glikokortykosteroidów wziewnych stanowią istotny element ich korzystnego oddziaływania w leczeniu astmy, szczególnie w zapobieganiu i leczeniu zaostrzeń astmy oraz oddziaływaniu na niektóre składowe remodelingu.Authors describe the clinical implications of nongenomic effects of glucocorticoids, important also for the inhaled drugs. Data suggest that these rapid actions of glucocorticoids are important in the pharmacotherapy of asthma, particularly for prevention and treatment of acute exacerbations. Their influence on remodeling is also considered

Variables posture in the sagittal plane in children attitude with scoliosis and idiopathic scoliosis

The aim of the study was to analyze the sagittal spinal curvatures in children with scoliosis and idiopathic scoliosis attitude and norm. The shape of the spine was assessed using optoelectronic Diers formetric III 4D. The research was Carried out in the Posturology Laboratory at the Faculty of Medicine and Health Sciences, UJK in Kielce (Poland). The biggest differences in the absolute values ​​of the variables tested in girls and boys with a group of scoliosis, attitudes and scoliotic standard body length was observed for SP-VP (mm). Univariate analysis of variance showed significant differences in the measurement of intra-lordosis angle among both boys and girls. This means that only the angles of lordosis differed significantly between the groups scoliosis, attitudes and scoliotic standard. Both girls and boys lordosis angle of scoliosis in the group was significantly lower than in the attitudes scolitic group and with the standard. In children with scoliosis it occurred in the first place to shallow lumbar lordosis. The size of the physiological thoracic kyphosis and lumbar lordosis should be taken into account in the selection of methods of treatment of scoliosis. In the treatment of scoliosis, use patterns shoulders and the pelvis, to restore the normal range thoracic kyphosis and lumbar lordosis

Assesment of antioxidative enzymes activity and intensification of lipids peroxidation in asthmatic patients.

Chronic immunoalergic in flammatory 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 oxygenic stress in asthma. It has been also shown that bacterial infection disturbes efficiency of antioxidative mechanisms. Pneumonol. Alergol. Pol. 2004, 72, 472-47

Guidelines of the Polish Respiratory Society for diagnosis and treatment of idiopathic pulmonary fibrosis

Introduction: This document presents the guidelines of the Polish Respiratory Society (PTChP, Polskie Towarzystwo Chorób Płuc) for diagnosis and treatment of idiopathic pulmonary fibrosis (IPF), developed by a group of Polish experts.Material and methods: The recommendations were developed in the form of answers to previously formulated questions concer-ning everyday diagnostic and therapeutic challenges. They were developed based on a current literature review using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.Results: We formulated 28 recommendations for diagnosis (8), pharmacological treatment (12) as well as non-pharma-cological and palliative therapy (8). The experts suggest that surgical lung biopsy (SLB) not be performed in patients with the probable usual interstitial pneumonia (UIP) pattern, with an appropriate clinical context and unanimous opinion of a  multidisciplinary team. The experts recommend using antifibrotic agents in IPF patients and suggest their use irrespective of the degree of functional impairment. As regards non-pharmacological and palliative treatment, strong re-commendations were formulated regarding pulmonary rehabilitation, oxygen therapy (in patients with chronic respiratory failure), preventive vaccinations as well as referring IPF patients to transplant centres. Table 1 presents an aggregate list of recommendations.Conclusions: The Polish Respiratory Society Working Group developed guidelines for IPF diagnosis and treatment

Molecular mechanisms of glucocorticoids action: implications for treatment of rhinosinusitis and nasal polyposis

Intra-nasal glucocorticoids are the most effective drugs available for rhinosinusitis and nasal polyposis treatment. Their effectiveness depends on many factors and not all of them have been well recognized so far. The authors present the basic information on molecular mechanisms of glucocorticoid action, direct and indirect effects of glucocorticoids on transcription of genes encoding inflammatory mediators. They focus on recently proved nongenomic mechanisms which appear quickly, from several seconds to minutes after glucocorticoid administration and discuss clinical implications resulting from this knowledge. Discovery of nongenomic glucocorticoid actions allows for better use of these drugs in clinical practice

Niegenomowy mechanizm działania glikokortykosteroidów

W pracy przedstawiono aktualną wiedzę dotyczącą mechanizmów działania glikokortykosteroidów (GK). Zgodnie z klasycznym modelem działania, określanym jako genomowy, GK wpływają (bezpośrednio lub pośrednio) na transkrypcję i translację genów kodujących mediatory procesu zapalnego. Aktualne badania podkreślają jednak znaczenie nietranskrypcyjnych oddziaływań GK, które ujawniają się szybko—od kilkunastu sekund do kilkunastu minut. W niegenomowym mechanizmie działania GK zasadniczą rolę odgrywają interakcje z receptorami GK zlokalizowanymi w cytoplazmie, ale przede wszystkim w błonie komórkowej, które aktywują wiele szlaków sygnałowych kinaz (MAPK, Src, PI3K) i kanałów jonowych, a także szlaki sygnałowe związane z receptorami sprzężonymi z białkiem G. Udowodniono także przekaz sygnału bez udziału receptora dla GK. Odkrycie niegenomowego mechanizmu GK pozwala lepiej zrozumieć ich przeciwzapalne i immunosupresyjne działanie

IL-6 Transsignaling in Patients with Chronic Spontaneous Urticaria.

IL-6 trans-signaling is critically involved in the initiation and promotion of inflammatory and autoimmune diseases. Therefore, we investigated the clinical relevance of soluble members of IL-6 trans-signaling system in chronic spontaneous urticaria (CSU).IL-6, interleukin 6 soluble receptor (IL-6 sR) and soluble gp130 (sgp130) were measured by ELISA method in plasma from CSU patients and the healthy subjects. The data were related to activation of the acute phase response as indicated by serum C-reactive protein (CRP) concentration and compared between patients stratified by the disease activity.Concentrations of IL-6, IL-6 sR, sgp130 in plasma and CRP in serum were significantly elevated in CSU patients compared with the healthy controls. CRP correlated significantly with IL-6 and sgp130, similarly IL-6 correlated significantly with sgp130. By contrast, CRP and IL-6 did not correlate significantly with IL-6 sR. However, significant correlation was noted between IL-6 sR and sgp130.Concentrations of IL-6 and its soluble receptors were significantly elevated in patients with CSU, suggesting upregulation of the IL-6 trans-signaling in the disease. In addition, our results support the concept that the system may be involved in pathogenesis of the systemic inflammatory activation in CSU patients