Изучение режима увлажнения засушливых районов Грузии с применением ком-плексного коэффициента влажности

შემოთავაზებულია ფორმულა, რომლის საფუძველზე გამოთვლილია სინოტივის კომპლექსური კოეფიციენტის მნიშვნელობები საქართველოს სხვადასხვა პუნქტისათვის მილებული მონაცემების მოხედვით აგებულია მისით ტერიტორიული განაწილების რუკა-სქემა რუკის საშუალებით შეიძლება განისაზღვროს სინოტივის ზონები.A formula is offered for calculation of humidity complex index, which has been determined for different points in Georgia. On the basis of obtained results a map is drown of the spatial distribution. Using this map the determination of humidity zones is possible.В работе предложена формула, по которой определены коэффициенты увлажнения для различных пунктов Грузии. На основе полученных данных построена карта-схема распределения этих параметров. С помошью карты определены зоны увлажнения

S-Adenosylmethionine Decreases Lipopolysaccharide-Induced Phosphodiesterase 4B2 and Attenuates Tumor Necrosis Factor Expression via cAMP/Protein Kinase A PathwayS⃞

S-Adenosylmethionine (SAM) treatment has anti-inflammatory, cytoprotective effects against endotoxin-induced organ injury. An important component of the anti-inflammatory action of SAM involves down-regulation of the lipopolysaccharide (LPS)-induced transcriptional induction of tumor necrosis factor-α (TNF) expression by monocytes/macrophages. We examined the effect of SAM on expression and activity of LPS-induced up-regulation of phosphodiesterase 4 (PDE4), which regulates cellular cAMP levels and TNF expression. LPS treatment of RAW 264.7, a mouse macrophage cell line, led to the induction of Pde4b2 mRNA expression with no effect on Pde4a or Pde4d. SAM pretreatment led to a significant decrease in LPS-induced up-regulation of Pde4b2 expression in both RAW 264.7 cells and primary human CD14+ monocytes. Of note, the decreased Pde4b2 mRNA expression correlated with the SAM-dependent increase in the transcriptionally repressive histone H3 lysine 9 trimethylation on the Pde4b2 intronic promoter region. The SAM-mediated decrease in LPS-inducible Pde4b2 up-regulation resulted in an increase in cellular cAMP levels and activation of cAMP-dependent protein kinase A (PKA), which plays an inhibitory role in LPS-induced TNF production. In addition, SAM did not affect LPS-inducible inhibitor of nuclear factor-κB degradation or nuclear factor-κB (NF-κB)-p65 translocation into the nucleus but rather inhibited NF-κB transcriptional activity. These results demonstrate for the first time that inhibition of LPS-induced PDE4B2 up-regulation and increased cAMP-dependent PKA activation are significant mechanisms contributing to the anti-TNF effect of SAM. Moreover, these data also suggest that SAM may be used as an effective PDE4B inhibitor in the treatment of chronic inflammatory disorders in which TNF expression plays a significant pathogenic role

The Unrecognized Effects of Phosphodiesterase 4 on Epithelial Cells in Pulmonary Inflammation

Acute pulmonary inflammation is characterized by migration of polymorphonuclear neutrophils (PMNs) into the different compartments of the lung, passing an endothelial and epithelial barrier. Recent studies showed evidence that phosphodiesterase (PDE) 4-inhibitors stabilized endothelial cells. PDE4B and PDE4D subtypes play a pivotal role in inflammation, whereas blocking PDE4D is suspected to cause gastrointestinal side effects. We thought to investigate the particular role of the PDE4-inhibitors roflumilast and rolipram on lung epithelium. Acute pulmonary inflammation was induced by inhalation of LPS. PDE4-inhibitors were administered i.p. or nebulized after inflammation. The impact of PDE4-inhibitors on PMN migration was evaluated in vivo and in vitro. Microvascular permeability, cytokine levels, and PDE4B and PDE4D expression were analyzed. In vivo, both PDE4-inhibitors decreased transendothelial and transepithelial migration even when administered after inflammation, whereas roflumilast showed a superior effect compared to rolipram on the epithelium. Both inhibitors decreased TNF$\alpha$, IL6, and CXCL2/3. CXCL1, the strong PMN chemoattractant secreted by the epithelium, was significantly more reduced by roflumilast. In vitro assays with human epithelium also emphasized the pivotal role of roflumilast on the epithelium. Additionally, LPS-induced stress fibers, an essential requirement for a direct migration of PMNs into the alveolar space, were predominantly reduced by roflumilast. Expression of PDE4B and PDE4D were both increased in the lungs by LPS, PDE4-inhibitors decreased mainly PDE4B. The topical administration of PDE4-inhibitors was also effective in curbing down PMN migration, further highlighting the clinical potential of these compounds. In pulmonary epithelial cells, both subtypes were found coexistent around the nucleus and the cytoplasm. In these epithelial cells, LPS increased PDE4B and, to a lesser extend, PDE4D, whereas the effect of the inhibitors was prominent on the PDE4B subtype. In conclusion, we determined the pivotal role of the PDE4-inhibitor roflumilast on lung epithelium and emphasized its main effect on PDE4B in hyperinflammation