Pre-feasibility analysis of an energy supply system for Southern Europe: Technical aspects

Technical aspects of the feasibility of energy transmission from hydroelectric power plants in Zaire to southern Europe, and to Italy in particular, have been studied. Three alternatives were considered: electric power transmission, gaseous hydrogen pipeline, and methylcyclohexane/toluene loop cycle. The technical feasibility of each alternative, also for a mid-term prospect, and energy losses were examined and evaluated. A comparison, from an energetic point of view, was also carried out among the three systems by varying the ratio between hydrogen and electric power required by the users. The high values of the energy transmission factor make this energy supply system very attractive. Depending on the sharing of the energy required for final uses, a double transportation system, based on electric power together with hydrogen, could be convenient. Indeed, if a very high amount of hydrogen is required by the users, a system based on hydrogen would be preferable.     

Serratiopeptidase Affects the Physiology of Pseudomonas aeruginosa Isolates from Cystic Fibrosis Patients

Pseudomonas aeruginosa is frequently involved in cystic fibrosis (CF) airway infections. Biofilm, motility, production of toxins and the invasion of host cells are different factors that increase P. aeruginosa’s virulence. The sessile phenotype offers protection to bacterial cells and resistance to antimicrobials and host immune attacks. Motility also contributes to bacterial colonization of surfaces and, consequently, to biofilm formation. Furthermore, the ability to adhere is the prelude for the internalization into lung cells, a common immune evasion mechanism used by most intracellular bacteria, such as P. aeruginosa. In previous studies we evaluated the activity of metalloprotease serratiopeptidase (SPEP) in impairing virulence-related properties in Gram-positive bacteria. This work aimed to investigate SPEP’s effects on different physiological aspects related to the virulence of P. aeruginosa isolated from CF patients, such as biofilm production, pyoverdine and pyocyanin production and invasion in alveolar epithelial cells. Obtained results showed that SPEP was able to impair the attachment to inert surfaces as well as adhesion/invasion of eukaryotic cells. Conversely, SPEP’s effect on pyocyanin and pyoverdine production was strongly strain-dependent, with an increase and/or a decrease of their production. Moreover, SPEP seemed to increase swarming motility and staphylolytic protease production. Our results suggest that a large number of clinical strains should be studied in-depth before drawing definitive conclusions. Why different strains sometimes react in opposing ways to a specific treatment is of great interest and will be the object of future studies. Therefore, SPEP affects P. aeruginosa’s physiology by differently acting on several bacterial factors related to its virulence.     

5 alpha-reductase inhibitors, chemical and clinical models

An active site model of 5 alpha-reductase type 2 isoenzyme on an "active-analog approach" and based on 4-azasteroidal inhibitors has been constructed to evaluate the effects on the inhibitory potency of substituents on the steroid A ring. This model has proven able to predict the potential inhibitory activity of 19-nor-10-azasteroid and 6-azasteroid compounds. A model for the evaluation of clinical efficacy of an inhibitor, based on in vitro data, has also been developed and applied to finasteride. This inhibitory potency evaluation of finasteride in human scalp homogenates, plus pharmacokinetic data, allows the calculation of a theoretical in situ inhibition value for human scalp. From the IC50 curve of finasteride in scalp homogenates, it is possible to calculate that for an inhibition level similar to that obtained in prostate with 5 mg of finasteride, the necessary plasma concentration of the drug is 1 microM, a level obtained after the acute administration of 50 mg of finasteride.     

Biochemical properties of amylase isozymes from Gammarus palustris. A comparative study

Two major alpha-amylase isozymes from Gammarus palustris were purified and characterized. These isozymes, Amy IW and Amy Ic, exhibit a seasonal pattern of expression. In this article we investigate whether the seasonal variation has an adaptive significance. In addition, the species-specific properties of amylases were studied. Purification of the isozymes was achieved by sequential glycogen-ethanol precipitation, Sephadex G-200 and ion exchange chromatography. Characterization in terms of Km, activity patterns at different temperatures, pH values and salt concentrations was done for both isozymes. In addition, the distribution of enzymatic products was analyzed in a high-performance liquid chromatography system. In all conditions tested, the two isozymes gave similar results. This observation suggests that the seasonal change in amylase expression pattern does not result in enzymes differentially suited for seasonal variation in conditions. A comparative analysis showed that G. palustris amylases are apparently distinct from other amylases. These distinctions were seen as an unusually low Km value, an activity peak at low NaCl concentration, a relatively high pH optimum and the predominant formation of maltotriose.     

Anti-Virulence Potential of a Chionodracine-Derived Peptide against Multidrug-Resistant Pseudomonas aeruginosa Clinical Isolates from Cystic Fibrosis Patients

Pseudomonas aeruginosa is an opportunistic pathogen causing several chronic infections resistant to currently available antibiotics. Its pathogenicity is related to the production of different virulence factors such as biofilm and protease secretion. Pseudomonas communities can persist in biofilms that protect bacterial cells from antibiotics. Hence, there is a need for innovative approaches that are able to counteract these virulence factors, which play a pivotal role, especially in chronic infections. In this context, antimicrobial peptides are emerging drugs showing a broad spectrum of antibacterial activity. Here, we tested the anti-virulence activity of a chionodracine-derived peptide (KHS-Cnd) on five P. aeruginosa clinical isolates from cystic fibrosis patients. We demonstrated that KHS-Cnd impaired biofilm development and caused biofilm disaggregation without affecting bacterial viability in nearly all of the tested strains. Ultrastructural morphological analysis showed that the effect of KHS-Cnd on biofilm could be related to a different compactness of the matrix. KHS-Cnd was also able to reduce adhesion to pulmonary cell lines and to impair the invasion of host cells by P. aeruginosa. A cytotoxic effect of KHS-Cnd was observed only at the highest tested concentration. This study highlights the potential of KHS-Cnd as an anti-biofilm and anti-virulence molecule against P. aeruginosa clinical strains.     

GMB: A tool for manipulating and animating graph data structures

This paper describes a tool graph originally developed for the Faust environment. Faust is a scientific program development environment being implemented at the Center for Supercomputing Research and Development at the University of Illinois at Urbana-Champaign. The graph tool comprises two major components: the Graph Manager that implements an abstract graph data type, and the Graph Browser that handles the details of displaying a subgraph of a graph created through the Graph Manager. The Graph Browser displays graph views, where a graph view is a subgraph of its parent graph. The concept of graph views is analogous to the concept of views in the traditional database sense. Several graph views may simultaneously exist for a single parent graph, where each view's subgraph depends on the context of the application requesting the view. Goals of the graph tool, GMB, included providing an abstract graph data type for general use and animating graphs efficiently.     

19-nor-10-azasteroids: a novel class of inhibitors for human steroid 5alpha-reductases 1 and 2

Steroid 5alpha-reductase is a system of two isozymes (5alphaR-1 and 5alphaR-2) which catalyzes the NADPH-dependent reduction of testosterone to dihydrotestosterone in many androgen sensitive tissues and which is related to several human endocrine diseases such as benign prostatic hyperplasia (BPH), prostatic cancer, acne, alopecia, pattern baldness in men and hirsutism in women. The discovery of new potent and selective 5alphaR inhibitors is thus of great interest for pharmaceutical treatment of these diseases. The synthesis of a novel class of inhibitors for human 5alphaR-1 and 5alphaR-2, having the 19-nor-10-azasteroid skeleton, is described. The inhibitory potency of the 19-nor-10-azasteroids was determined in homogenates of human hypertrophic prostates toward 5alphaR-2 and in DU-145 human prostatic adenocarcinoma cells toward 5alphaR-1, in comparison with finasteride (IC50 = 3 nM for 5alphaR-2 and approximately 42 nM for 5alphaR-1), a drug which is currently used for BPH treatment. The inhibition potency was dependent on the type of substituent at position 17 and on the presence and position of the unsaturation in the A and C rings. delta9(11)-19-Nor-10-azaandrost-4-ene-3,17-dione (or 10-azaestra-4,9(11)-diene-3,17-dione) (4a) and 19-nor-10-azaandrost-4-ene-3,17-dione (5) were weak inhibitors of 5alphaR-2 (IC50 = 4.6 and 4.4 microM, respectively) but more potent inhibitors of 5alphaR-1 (IC50 = 263 and 299 nM, respectively), whereas 19-nor-10-aza-5alpha-androstane-3,17-dione (7) was inactive for both the isoenzymes. The best result was achieved with the 9:1 mixture of delta9(11)- and delta8(9)-17beta-(N-tert-butylcarbamoyl)-19-nor-10-aza-4- androsten-3-one (10a,b) which was a good inhibitor of 5alphaR-1 and 5alphaR-2 (IC50 = 127 and 122 nM, respectively), with a potency very close to that of finasteride. The results of ab initio calculations suggest that the inhibition potency of 19-nor-10-azasteroids could be directly related to the nucleophilicity of the carbonyl group in the 3-position.