15 (S)-HETE modulates LTB4 production and neutrophil chemotaxis in chronic bronchitis

We evaluated the levels of 15(S)-hydroxyeicosatetraenoic acid [15(S)-HETE] and the expression of 15-lipoxygenase (15-LO) mRNA in induced sputum obtained from 10 control and 15 chronic bronchitis subjects. 15(S)-HETE was evaluated by reverse phase high-performance liquid chromatography separation followed by specific RIA. 15-LO mRNA expression was determined by primed in situ labeling. The levels of both soluble and cell-associated 15(S)-HETE resulted significantly higher in chronic bronchitis than in control subjects. The percentage of cells expressing 15-LO mRNA was significantly higher in chronic bronchitis than in control subjects (P < 0.01). Double staining for specific cell type markers and 15-LO mRNA showed macrophages and neutrophils positive for 15-LO, whereas similar staining of peripheral blood neutrophils did not show evidence for 15-LO expression, suggesting that expression of 15-LO in neutrophils takes place on migration into the airways. Because 15(S)-HETE inversely correlated with the percentage of neutrophils in sputum of chronic bronchitis subjects, we studied the effect of 15(S)-HETE on leukotriene B4 (LTB4) production in vitro and evaluated the concentration of LTB4 in induced sputum and the contribution of LTB4 to the chemotactic activity of induced sputum samples ex vivo. The results obtained indicate that macrophages and neutrophils present within the airways of chronic bronchitis subjects express 15-LO mRNA; increased basal levels of 15(S)-HETE may contribute to modulate, through the inhibition of 5-lipoxygenase metabolites production, neutrophil infiltration and airway inflammation associated with chronic bronchitis

Leukotriene B4 production in human mononuclear phagocytes is modulated by interleukin-4-induced 15-lipoxygenase

The aim of this study was to evaluate the consequences of interleukin (IL)-4-induced 15-lipoxygenase (15-LO) expression on leukotriene B4 (LTB4) synthesis in human monocytes. Human monocytes incubated for 24, 48, and 72 h with IL-4 (10 ng/ml) were stimulated with Ca2+-ionophore A23187 (calcimycin; 5 \u3bcM) or opsonized zymosan. 15(S)-hydroxyeicosatetraenoic acid [15(S)-HETE], LTB4, and arachidonic acid (AA) release were measured by high-performance liquid chromotography/radioimmunoassay, liquid chromotography/tandem mass spectrometry (LC/MS/MS), or gas chromatography/mass spectrometry. 15-LO activity was evaluated in AA-treated monocytes. 15-LO, 5-lipoxygenase (5-LO) and 5-LO activating protein (FLAP) expression were analyzed by reverse transcription-polymerase chain reaction. Neutrophil chemotactic activity was evaluated using a microtaxis chamber assay. A23187-induced synthesis of 15(S)-HETE was significantly increased after treatment with IL-4 (10 ng/ml) for 48 and 72 h (p < 0.001). Concomitant decrease of LTB4 release was observed after 72 h of incubation with IL-4 (p < 0.001). LC/MS/MS analysis confirmed the production of 15(S)-HETE and the significant inhibition of LTB4 synthesis in IL-4-treated monocyte after challenge with opsonized zymosan. IL-4 treatment induced 15-LO enzymatic activity as well as 15-LO mRNA, but did not affect either 5-LO or FLAP mRNA expression in monocytes. Supernatant from IL-4-treated monocytes showed significantly lower neutrophil chemotactic activity than controls. 15(S)-HETE significantly inhibited LTB4 production induced by A23187-stimulated human monocytes without affecting AA release. IL-4-induced expression of 15-LO in monocytes caused a significant reduction of LTB4 production. Whereas this effect did not reflect changes in 5-LO and FLAP mRNA expression, synthetic 15(S)-HETE was able to significantly inhibit the synthesis of LTB4, without affecting AA release

Traumatic brain injury in an aging population

The epidemiology of traumatic brain injury (TBI) is changing in several Western countries, with an increasing proportion of elderly TBI patients admitted to the intensive care unit (ICU). We describe a series of 1366 adult patients admitted to three neuro-ICUs in which 44% of cases were 50 years of age or older. The health status before trauma (rated using the APACHE score) was worse in older patients. In all 604 patients had emergency removal of intracranial masses, with extradural hematomas more frequent in young cases and subdural hematomas more frequent in older patients. Outcomes were classified according to the Glasgow Outcome Scale (GOS) 6 months post-trauma, as favorable (GOS score 4-5), or unfavorable (GOS score 1-3). Favorable outcomes were achieved by 50% of patients, but the proportions of unfavorable outcomes rose with age. Mortality was the main cause of unfavorable outcomes 6 months after injury in older patients. Logistic regression analysis indicates that several parameters independently contributed to outcome, including the motor component of the Glasgow Coma Scale (GCS), pupils, CT findings, and early hypotension. Additionally, the odds ratios were very high for age and health status before TBI. Patients admitted to the ICU are increasingly older, have co-morbidities, and have specific types of intracranial lesions. Early rescue, surgical treatment, and intensive care of these patients may produce excellent results up to the age of 59 years, with favorable outcomes still possible for 39% of cases aged 60-69 years, without an excessive burden of severely disabled patients

Prediction of ionic liquid's heat capacity by means of their in silico principal properties

The in silico principal properties (PPs) of ionic liquids (ILs), derived by means of the VolSurf+ approach, were used to develop a Partial Least Squares (PLS) model able to find a quantitative correlation among IL descriptors (accounting for both cationic and anionic structural features) and heat capacity values, providing affordable predictions validated by experimental Cp measurements for an external set of ILs. In silico predictions allowed the selection of a limited number of structurally different ILs with similar Cp values, providing the possibility to select an optimal IL according to efficiency, as well as to environmental and economic sustainability. The present general procedure, using readily available descriptors for above 8000 ILs and adopting an accessible statistical procedure such as PLS, could be extended to other QSPR models

Analysis of the new submarine interconnection system between Italy and Malta: Simulation of transmission network operation

In this paper, some simulations of the interconnected Sicilian and Maltese transmission systems are performed, in order to assess this new system configuration. The HVAC submarine interconnection between Italy and Malta came into operation in 2015 and is part of a European programme for transmission grid interconnection improvement. This new line has been built in order to allow a better management of the power system of both the islands. Firstly, a brief description of the interconnection system is given. Moreover, the transmission systems of Sicily and Malta are depicted and their structures are shown. The simulations are carried out by means of a model of the interconnected system created on purpose on NEPLAN\uae environment. Some working scenarios are assumed in order to perform load flow calculation and to highlight the effects of power export towards Malta. In order to find the contribution to the power exported through the interconnection line, a power flows tracing method is implemented. The results show that the Sicily-Malta interconnection makes possible a significant improvement of RES exploitation in Sicily, a better management of Sicilian traditional plants and a reduction of the polluting emissions from the two obsolete Maltese fuel oil thermal plants

A Matrix Model For An Energy Management System Based On Multi-Carrier Energy Hub Approach

The INGRID FP7 European co-funded project studies several methodologies concerning hydrogen production and storage, aiming to provide services to electricity system operators for suitably balancing electrical supply and demand. In such a context, the problem of integrating different carriers into a single multi-hub optimiser represents a challenging topic for the research. This paper depicts the Energy Management System (EMS) of the plant which will be developed and built as a prototype of the INGRID system. The approach followed for the EMS design and development takes the cue from the matrix model presented in the rest of the paper, as well as the general optimisation problem formulation and the algorithm selected for its solution

Urban Energy Hubs and Microgrids: Smart Energy Planning for Cities

In this chapter, we try to connect the urban design features with energy consumption and consequent pollution parameters. After a review of a selected set of approaches to Urban Energy Systems study with a special focus on electrical power systems, urban energy systems are proposed as networks of multi-source hybrid energy hubs, where different energy flows are collected at the same bus and can be stored, delivered or transformed as needed. Resources at the hub and infrastructures interact with each other; therefore, both definition and boundaries of such energy systems at urban level are difficult to be clearly outlined. Similarly, the possibility to generate new operational models based on existing critical urban infrastructures is also challenging. This contribution proposes a preliminary study of urban energy hubs. Operations of thermal, electrical and mobility infrastructures are considered as qualifying features of the hub, but still the interconnected operation is not taken into account. The application part shows, indeed, the analysis and optimized design of the energy system serving two different urban districts. The related optimized parametric design of power generation infrastructures is considered as a function of urban features. The results about emissions and costs provide some interesting conclusions about the linkage between energy planning and urban features at district level, thus allowing, as possible application of this work, an energy-based territorial planning for urban contexts

15-Lipoxygenase expression and 15 (S)-hydroxyeicoisatetraenoic acid release and reincorporation in induced sputum of asthmatic subjects

Background: Recent evidence shows that 15(S)-hydroxyeicoisatetraenoic acid (15[S]-HETE) can be released and rapidly reincorporated into cellular lipids. These mechanisms exert several immunoregulatory functions that may be relevant in airway inflammation. Objective: Our purpose was to evaluate the levels of both soluble and cell-associated 15(S)-HETE and to examine 15- lipoxygenase (15-LO) messenger RNA (mRNA) expression in sputum samples obtained from 10 control and 18 asthmatic subjects. Methods: Levels of 15(S)- HETE were measured by reverse-phase HPLC separation followed by RIA in supernatants and in cell membrane-extracted phospholipids after acid hydrolysis. 15-LO mRNA was evaluated by primed in situ hybridization (PRINS). Combined immunocytochemistry and PRINS was used to identify the phenotype of cells bearing 15-LO transcripts. Results: Levels of both soluble and cell- associated 15(S)-HETE were higher in asthmatic than in control subjects (P < .0001). The percentage of cells expressing 15-LO mRNA was higher in asthmatic than in control subjects (P < .01). On double staining for specific cell-type markers and 15-LO mRNA, macrophages were the major source for 15-LO. Conclusion: This study shows that the induced sputum technique allows the evaluation of 15-LO activity and that soluble, cell-associated 15(S)-HETE and 15-LO levels are higher in asthmatic than in control subjects. In addition, this study indicates that, in induced sputum, airway macrophages are the major source of 15(S)-HETE in asthma