Engineered Liposomes Protect Immortalized Immune Cells from Cytolysins Secreted by Group A and Group G Streptococci.

The increasing antibiotic resistance of bacterial pathogens fosters the development of alternative, non-antibiotic treatments. Antivirulence therapy, which is neither bacteriostatic nor bactericidal, acts by depriving bacterial pathogens of their virulence factors. To establish a successful infection, many bacterial pathogens secrete exotoxins/cytolysins that perforate the host cell plasma membrane. Recently developed liposomal nanotraps, mimicking the outer layer of the targeted cell membranes, serve as decoys for exotoxins, thus diverting them from attacking host cells. In this study, we develop a liposomal nanotrap formulation that is capable of protecting immortalized immune cells from the whole palette of cytolysins secreted by Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis-important human pathogens that can cause life-threatening bacteremia. We show that the mixture of cholesterol-containing liposomes with liposomes composed exclusively of phospholipids is protective against the combined action of all streptococcal exotoxins. Our findings pave the way for further development of liposomal antivirulence therapy in order to provide more efficient treatment of bacterial infections, including those caused by antibiotic resistant pathogens

Membrane Cholesterol Regulates Smooth Muscle Phasic Contraction

The regulation of contractile activity in smooth muscle cells involves rapid discrimination and processing of a multitude of simultaneous signals impinging on the membrane before an integrated functional response can be generated. The sarcolemma of smooth muscle cells is segregated into caveolar regions-largely identical with cholesterol-rich membrane rafts—and actin-attachment sites, localized in non-raft, glycerophospholipid regions. Here we demonstrate that selective extraction of cholesterol abolishes membrane segregation and disassembles caveolae. Simultaneous measurements of force and [Ca2+]i in rat ureters demonstrated that extraction of cholesterol resulted in inhibition of both force and intracellular Ca2+ signals. Considering the major structural reorganization of cholesterol-depleted sarcolemma, it is intriguing to note that decreased levels of membrane cholesterol are accompanied by a highly specific inhibition of phasic, but not tonic contractions. This implies that signalling cascades that ultimately lead to either phasic or tonic response may be spatially segregated in the plane of the sarcolemma. Replenishment of cholesterol restores normal contractile behavior. In addition, the tissue function is re-established by inhibiting the large-conductance K+-channel. Sucrose gradient ultracentrifugation in combination with Western blotting analysis demonstrates that its α-subunit is associated with detergent-resistant membranes, suggesting that the channel might be localized within the membrane rafts in vivo. These findings are important in understanding the complex signalling pathways in smooth muscle and conditions such as premature labor and hypertensio

Effect of low temperatures on osserous and cartilaginous tissues

The use of extreme cold to treat tumoral afflictions of the extremities is discussed. Cryogenic methods and instruments are discussed, and the levels of accumulated knowledge in this area (as well as the areas still in question) are evaluated. The overall promise for cryogenic methods of treatment is acknowledged, and areas which need further development are noted

The annexins: spatial and temporal coordination of signaling events during cellular stress

Annexins are a family of structurally related, Ca2+-sensitive proteins that bind to negatively charged phospholipids and establish specific interactions with other lipids and lipid microdomains. They are present in all eukaryotic cells and share a common folding motif, the "annexin core”, which incorporates Ca2+- and membrane-binding sites. Annexins participate in a variety of intracellular processes, ranging from the regulation of membrane dynamics to cell migration, proliferation, and apoptosis. Here we focus on the role of annexins in cellular signaling during stress. A chronic stress response triggers the activation of different intracellular pathways, resulting in profound changes in Ca2+ and pH homeostasis and the production of lipid second messengers. We review the latest data on how these changes are sensed by the annexins, which have the ability to simultaneously interact with specific lipid and protein moieties at the plasma membrane, contributing to stress adaptation via regulation of various signaling pathway

The expression levels of three raft-associated molecules in cultivated vascular cells are dependent on culture conditions

Relaying a signal across the plasma membrane requires functional connections between the partner molecules. Membrane microdomains or lipid rafts provide an environment in which such specific interactions can take place. The integrity of these sites is often taken for granted when signalling pathways are investigated in cell culture. However, it is well known that smooth muscle and endothelial cells undergo cytoskeletal rearrangements during monolayer culturing. Likewise affected - and with potentially important consequences for signalling events - is the organization of the plasma membrane. The expression levels of three raft markers were massively upregulated, and raft-associated 5′-nucleotidase activity increased in conventional monolayer cultures as compared with a spheroidal coculture model, shown to promote the differentiation of endothelial cells. Our data point to a shift of raft components in monolayer cultures and demonstrate potential advantages of the spheroid coculture system for investigation of raft-mediated signalling events in endothelial cell

Підходи до формування вартості будівельних робіт виконуваних вітчизняними будівельними підприємствами за межами України

The article defines approaches to the formation of the cost of construction works performed by domestic construction companies outside Ukraine. The authors conclude that the formation of a competitive price for finished construction products or for separate construction works (services) abroad is often associated with the emergence of additional costs incurred by the contractors due to the specifics of exports (for travel, accommodation, transport costs for the delivery of construction equipment , costs for obtaining various approvals and permits, etc.).У статті визначаються підходи до формування вартості будівельних робіт виконуваних вітчизняними будівельними підприємствами за межами України. Автори роблять висновок про те, що формування конкурентної ціни на готову будівельну продукцію або на окремі будівельні роботи (послуги) за кордоном часто пов'язане з виникненням у підрядників додаткових витрат викликаних специфікою експорту (на відрядження, оплатою проживання, транспортними витратами на доставку будівельної техніки, витратами на отримання різних погоджень та дозволів і ін.)

Clinical Streptococcus pneumoniae isolates induce differing CXCL8 responses from human nasopharyngeal epithelial cells which are reduced by liposomes

BACKGROUND: Streptococcus pneumoniae causes several human diseases, including pneumonia and meningitis, in which pathology is associated with an excessive inflammatory response. A major inducer of this response is the cholesterol dependent pneumococcal toxin, pneumolysin. Here, we measured the amount of inflammatory cytokine CXCL8 (interleukin (IL)-8) by ELISA released by human nasopharyngeal epithelial (Detroit 562) cells as inflammatory response to a 24 h exposure to different pneumococcal strains. RESULTS: We found pneumolysin to be the major factor influencing the CXCL8 response. Cholesterol and sphingomyelin-containing liposomes designed to sequester pneumolysin were highly effective at reducing CXCL8 levels from epithelial cells exposed to different clinical pneumococcal isolates. These liposomes also reduced CXCL8 response from epithelial cells exposed to pneumolysin knock-out mutants of S. pneumoniae indicating that they also reduce the CXCL8-inducing effect of an unidentified pneumococcal virulence factor, in addition to pneumolysin. CONCLUSION: The results indicate the potential of liposomes in attenuating excessive inflammation as a future adjunctive treatment of pneumococcal diseases

Концесія як найбільш ефективна форма розвитку морських торгівельних портів України

Бабійчук А. В. Концесія як найбільш ефективна форма розвитку морських торгівельних портів України / А. В. Бабійчук // Економіко-правовий розвиток сучасної України : матер. ІIІ Всеукр. наук. конф. студ., аспір. та молодих вчених (22-23 листопада 2013 р., м. Одеса) / за ред. д.е.н., проф. О. М. Кібік, д.ю.н., проф. О. П. Подцерковного ; Національн. ун-т «Одеська юридична академія» – Одеса : Фенікс, 2013. – С. 310-312

ВИБІР ТАКТИКИ ЛІКУВАННЯ УСКЛАДНЕНИХ ФОРМ ЖОВЧНОКАМ’ЯНОЇ ХВОРОБИ У ПОХИЛОМУ І СТАРЕЧОМУ ВІЦІ

The article adduces the results of surgical treatment of 380 patients with complicated forms of the gallstone disease (GSD). The complicated course of an acute calculous cholecystitis was observed in 149 (39.2 %) patients, and chronic one was in 136 (35.8 %) patients. Bile duct pathology was diagnosed in 95 (25.0 %) patients. Мinimally invasive surgical interferences were performed in 320 (84.2 %) patients, and open surgical interferences were performed in 60 (15.8 %) patients. Complications following after minimally invasive surgical interferences were observed in 4 (1.2 %) cases, and after open surgical interferences were in 6 (10.0 %) cases. 2 (3.3 %) patients died. The results of the study demonstrated that minimally invasive surgical interferences in complicated forms of the GSD in elderly and senile patients are with highest priority.У статті представлено результати хірургічного лікування 380 хворих на ускладнені форми жовчнокам’яної хвороби (ЖКХ). Ускладнений перебіг гострого калькульозного холециститу спостерігався у 149 (39,2 %) пацієнтів, хронічного – у 136 (35,8 %). Патологію жовчних проток діагностовано у 95 (25,0 %) хворих. Малоінвазивні операційні втручання проведено у 320 (84,2 %) пацієнтів, відкриті – у 60 (15,8 %). Ускладнення після малоінвазивних втручань спостерігали у 4 (1,2 %) хворих, після відкритих – у 6 (10,0 %). Померли 2 (3,3 %) пацієнти. За результатами проведеного дослідження показано, що застосування малоінвазивних втручань при ускладнених формах ЖКХ у хворих похилого і старечого віку є пріоритетним