A persistent, chronic dry cough is the most common adverse effect of angiotensin converting enzyme (ACE) inhibitors therapy. The mechanism of this respiratory adverse effect is related to the inhibition of ACE and the accumulation of bradykinin, substance P, prostanoids and other inflammatory neuropeptides in the airways. The aim of this study was to follow the relationship between 15-day administration of enalapril and the defense reflexes (cough and bronchoconstriction) of the airways in experimental animals, as well as the possibility of their pharmacological restriction with simultaneous diltiazem administration. Cough reflex was investigated by the method of mechanical irritation of laryngopharyngeal and tracheobronchial area in non-anesthetized cats. The reactivity of tracheal smooth muscles of the airways to bronchoconstrictor mediators (histamine 10 nM – 1 mM, acetylcholine 10 nM – 1 mM and KCl 1 mM – 100 mM) was evaluated by an in vitro method in guinea pigs. Enalapril 5 mg/kg/day and diltiazem 30 mg/kg/day were administered perorally for 15 days. The results showed that long-lasting administration of enalapril resulted in a significant increase of measured cough parameters and increased reactivity of tracheal smooth muscle to histamine and KCl. Simultaneous administration of enalapril together with diltiazem significantly decreased the enalapril induced cough, and decreased enalapril induced hyperreactivity of tracheal smooth muscles to KCl. The results showed a partially protective effect of diltiazem and enalapril co-administration on the respiratory adverse effects induced by enalapril therapy.
Nitric oxide (NO) is an important endogenous neurotransmitter and mediator. It participates in regulation of physiological processes in different organ systems including airways. Therefore, it is important to clarify its role in the regulation of both airway and vascular smooth muscle, neurotransmission and neurotoxicity, mucus transport, lung development and in the surfactant production. The bioactivity of NO is highly variable and depends on many factors: the presence and activity of NO-producing enzymes, activity of competitive enzymes (e.g. arginase), the amount of substrate for the NO production, the presence of reactive oxygen species and others. All of these can change NO primary physiological role into potentially harmful. The borderline between them is very fragile and in many cases not entirely clear. For this reason, the research focuses on a comprehensive understanding of NO synthesis and its metabolic pathways, genetic polymorphisms of NO synthesizing enzymes and related effects. Research is also motivated by frequent use of exhaled NO monitoring in the clinical manifestations of respiratory diseases. The review focuses on the latest knowledge about the production and function of this mediator and understanding the basic physiological processes in the airways., M. Antosova, D. Mokra, L. Pepucha, J. Plevkova, T. Buday, M. Sterusky, A. Bencova., and Obsahuje bibliografii
Thyroid nodules are a very frequent pathology among common population. Despite the vast majority of them are of benign origin, the incidence of thyroid cancer is currently rather rising. Although there are several risk factors of thyroid cancer and several clinical, ultrasound, biochemical and molecular diagnostic markers, the exact mechanisms of thyroid oncogenesis and the linkage between thyroid nodule ultrasound appearance and its biological character remain unclear. While ionizing radiation is the only one well-known risk factor for thyroid cancer, the significance of some others remains unclear. The aim of our review was to discuss some not completely known pathophysiological mechanisms involved in thyroid oncogenesis as hypothyroidism, mutations of genes regulating cell proliferation, thyroid autoimmunity and pregnancy and to describe pathophysiological background of some ultrasound markers of thyroid cancer (size, echogenicity, vascularization, calcifications and stiffness). Better knowledge in this field is crucial for development of novel diagnostic techniques and therapeutic approaches. For exampl e, the analysis of BRAF, RAS and other mutations in cytological samples may help to distinction between follicular thyroid carcinoma and follicular thyroid adenoma and may signific antly decrease the number of unnecessary surgery among patients with thyroid nodules. Alternatively, the different malign cells growth, angiogenesis, destructions of thyroid follicles, reparative changes, growth retardation, fibrosis and increased interstitial fluid pressure implicate the typical ultrasound appearance of papillary thyroid cancer (hypoechogenicity, irregular vascularization, microcalcifications, stiffness) which is essential to catch the suspicious nodules on the basis of their ultrasound appearance among large amount of benign nodules., J. Krátký, H. Vítková, J. Bartáková, Z. Telička, M. Antošová, Z. Límanová, J. Jiskra., and Obsahuje bibliografii