1498 Majority of the above-mentioned action of GCs is mediated by interactions with intracellular cytoplasmic receptors, leading to the production of protein with specific regulatory functions. In these genomically mediated pro- cesses, transcription and translation with subsequent pro- teosynthesis requires at least several hours until some changes may be observed on the systemic level. However, GCs act also through nongenomically mediated mecha- nisms, which are responsible for rapid GCs action until the effects mediated by genomic mechanisms occur [71]. In literature, three possible nongenomic mechanisms are discussed (Fig. 1): specific interaction with cytosolic GC receptors (cGCR) and successive release of HSP90 and special proteins Src and MAPK, non-specific interactions with cellular membranes and specific interactions with membrane-bound glucocorticoid receptors. GCs may exert rapid effects on various tissues and cells, modulating hormone secretion, neuronal excitability, carbohydrate metabolism, cell morphology, cell behaviour and other processes within seconds or minutes [23, 71]. The GC action may be related to affecting ion cycling [81], cellular energy metabolism [8] or neuronal activity [12], as well as to rapid effects on second messenger systems [8]. In the respiratory system, GCs presumably via nongenomic action modulated Na+/H+ exchange activity in bronchial epithelial cells [81] and inhibited airway smooth muscle contraction within 10 min after GCs inhalation [73, 91]. Similarly, in a rabbit model of MAS, GCs already significantly improved several respiratory parameters within 30 min after the administration [50, 51]. In addition, interactions between genomic and non- genomic mechanisms have been claimed, thereby control- ling genomic mechanisms through nongenomic ones [85]. Nongenomic effects occur faster and may be clinically relevant over a limited period, “bridging the gap” until the long-term genomic effects take place [9]. Irrespective of the mechanisms of their action, GCs may effectively suppress polymorphonuclear inflammation, lung edema formation and pulmonary vasoconstriction. Howev- er, the effect of the treatment depends on the specific properties, dose and mode of delivery of the individual GCs as well as on the current status of the newborn or experimental animal with MAS. Glucocorticoids in the treatment of MAS Despite GCs having been used in various animal models of MAS as well as in several clinical studies, some questions still remain unanswered. Particularly: 1. According to the pharmacological properties, which of the available synthetic GC preparations is the best choice—i.e. most effective with low side effects? Eur J Pediatr (2011) 170:1495–1505 2. What way of GCs administration is better—intravenous or intratracheal? 3. What dosing and timing should be used? When to administer GCs and in what dose per individual GCs preparation? Is it better to use single or repetitive doses of the GC preparative? 4. Is it possible to combine GCs with other drugs emphasizing their favourable effects? Pharmacological properties of GCs preparations Individual GCs may exert different pharmacological prop- erties including different mineralocorticoid activity. Al- though accepted in practice, the clinical potencies of GC preparations have been difficult to assess using classical approaches. For example, the potency of GCs to suppress cortisol production does not sufficiently reflect the ability to suppress inflammation [21]. In addition, it is suggested that different GCs may have different potency per target tissue. The basic characteristics of commonly prescribed GCs preparations are listed in Table 1. In addition, regarding their nongenomic action, the relative drug potency of individual GCs may differ from the hierarchy for the classic genomic effects. For example, assessing some rapid nongenomic effects, dexamethasone was shown to be the most potent among the tested GCs, thanks probably to the lowest lipophilicity facilitating its interaction directly with the cell membrane [9, 46, 64, 79]. Side effects of GCs The administration of GCs may be accompanied by mostly unwanted side effects due to their influencing the physiolog- ical processes in the body. The occurrence and intensity of adverse effects depend on the type of GCs preparation, dosing, timing and way of administration. While adverse effects are rare in the administration of low (“physiological” or “substitutional”) doses of GCs in substitution therapy, the long-term administration of high (“pharmacological” or “supraphysiological”) doses of GCs may be associated with the side effects of various characters. GC drugs suppress the function of the hypothalamic–pituitary–adrenal axis, decreas- ing the secretion of corticotropin, which in turn reduces the secretion of cortisol by adrenal glands. Prolonged adrenal suppression may cause reduced responses to stress [3]. In addition, long-term GCs administration may lead to hyper- glycaemia, hypokalemia, dyslipidemia, reduced fibrinolysis, hypertension, posterior subcapsular cataract, exacerbation of glaucoma, increased intracranial pressure, peptic ulcers, upper gastrointestinal bleeding, immunosuppression, neuro- psychiatric disturbances, osteoporosis, myopathy, irregulari- ties of the menstruation cycle, etc. [63].