The respiratory system is constantly exposed to pathogens which enter the lungs by inhalation or via blood stream. Lipopolysaccharide (LPS), also named endotoxin, can reach the airspaces as the major component of the outer membrane of Gram-negative bacteria, and lead to local inflammation and systemic toxicity. LPS affects alveolar type II (ATII) cells an d pulmonary surfactant and although surfactant molecule has the effective protective mechanisms, excessive amount of LPS interacts with surfactant film and leads to its inactivation. From immunological point of view, surfactant specific proteins (SPs) SP-A and SP-D are best characterized, however, there is increasing evidence on the involvement of SP-B and SP-C and certain phospholipids in immune reactions. In animal models, the instillation of LPS to the respiratory system induces acute lung injury (ALI). It is of clinical importance that endotoxin-induced lung injury can be favorably influenced by intratracheal instillation of exogenous surfactant. The beneficial effect of this treatment was confirmed for both natural porcine and synthetic surfactants. It is believed that the surfactant preparations have anti-inflammatory properties through regulating cytokine production by inflammatory cells. The mechanism by which LPS interferes with ATII cells and surfactant layer, and its consequences are discussed below., M. Kolomaznik, Z. Nova, A. Calkovska., and Obsahuje bibliografii
Major depressive disorder is associated with abnormal autonomic regulation which could be noninvasively studied using pupillometry. However, the studies in adolescent patients are rare. Therefore, we aimed to study the pupillary light reflex (PLR), which could provide novel important information about dynamic balance between sympathetic and parasympathetic nervous system in adolescent patients suffering from major depression. We have examined 25 depressive adolescent girls (age 15.2±0.3 y ear) prior to pharmacotherapy and 25 age/gender-matched healthy subjects. PLR parameters were measured separately for both eyes after 5 min of rest using Pupillometer PLR-2000 (NeurOptics, USA). The constriction percentual change for the left eye was significantly lower in depressive group compared to control group (-24.12±0.87 % vs. - 28.04±0.96%, p˂0.01). Furthermore, average constriction velocity and maximum constriction velocity for the left eye were significantly lower in depressive group compared to control group (p˂0.05, p˂0.01, respectively). In contrast, no significant between-groups differences were found for the right eye. Concluding, this study revealed altered PLR for left eye indicating a deficient parasympathetic activity already in adolescent major depression. Additionally, the differences between left and right eye could be related to functional lateralization of autonomic control in the central nervous system., A. Mestanikova, I. Ondrejka, M. Mestanik, D. Cesnekova, Z. Visnovcova, I. Bujnakova, M. Oppa, A. Calkovska, I. Tonhajzerova., and Obsahuje bibliografii
Meconium aspiration syndrome (MAS) in newborns is characterized mainly by respiratory failure due to surfactant dysfunction and inflammation. Previous meta-analyses did not prove any effect of exogenous surfactant treatment nor glucocorticoid administration on final outcome of children with MAS despite oxygenation improvement. As we supposed there is the need to intervene in both these fields simultaneously, we evaluated therapeutic effect of combination of exogenous surfactant and selective inhibitor of NF-κB (IKK-NBD peptide). Young New Zealand rabbits were instilled by meconium suspension and treated by surfactant alone or surfactant in combination with IKK-NBD, and oxygen-ventilated for 5 h. PaO2/FiO2, oxygenation index, oxygen saturation and ventilation efficiency index were evaluated every hour; post mortem, total and differential leukocyte counts were investigated in bronchoalveolar lavage fluid (BALF) and inflammatory, oxidative and apoptotic markers were assessed in lung tissue homogenates. Exogenous surfactant combined with IKK-NBD improved oxygenation, reduced neutrophil count in BALF and levels of IL-1β, IL-6, p38 MAPK and caspase 3 in comparison with surfactant-only therapy. It seems that inhibition of inflammation may be strong supporting factor in surfactant treatment of MAS., J. Kopincova, P. Mikolka, M. Kolomaznik, P. Kosutova, A. Calkovska, D. Mokra., and Obsahuje bibliografii
Inflammation and other immune responses are involved in the variety of diseases and disorders. The acute response to endotoxemia includes activation of innate immune mechanisms as well as changes in autonomic nervous activity. The autonomic nervous system and the inflammatory response are intimately linked and sympathetic and vagal nerves are thought to have anti-inflammation functions. The basic functional circuit between vagus nerve a nd inflammatory response was identified and the neuroimmunomodulation loop was called cholinergic anti-inflammatory pathway. Unique function of vagus nerve in the anti-inflammatory reflex arc was found in many experimental and pre-clinical studies. They br ought evidence on the cholinergic signaling interacting with systemic and local inflammation, particularly suppressing immune cells function. Pharmacological/electrical modulation of vagal activity suppressed TNF-α and other proinflammatory cytokines prod uction and had beneficial therapeutic effects. Many questions related to mapping, linking and targeting of vagal-immune interactions have been elucidated and brought understanding of its basic physiology and provided the initial support for development of Tracey's inflammatory reflex. This review summarizes and critically assesses the current knowledge defining cholinergic anti-inflammatory pathway with main focus on studies employing an experimental approach and emphasizes the potential of modulation of va gally-mediated anti-inflammatory pathway in the treatment strategies., I. Zila, D. Mokra, J. Kopincova, M. Kolomaznik, M. Javorka, A. Calkovska., and Obsahuje bibliografii