Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder, characterized by the formation, aggregation and accumulation of amyloid beta, perturbed metal (copper, iron and zinc) homeostasis, metal-induced oxidative stress, neuroinflammation, aberrant activity of acetylcholinesterase (AChE) and other pathologies. The aim of this review is to discuss the current therapies based on the “combination-drugs-multitargets” strategy to target multiple pathologies to block the progression of pathogenesis of AD. In addition to cholinergic and amyloid targets, a significant effort is focused on targeting the metal-induced oxidative stress component of the disease. The main focus of research is based on modifications of existing drugs with specific biological activity. Tacrine was the first AChE inhibitor to be introduced into clinical practice and has been frequently used for the design of multitarget-directed ligands. A number of hybrid compounds containing tacrine and structural moieties derived from natural sources such as flavonoids [quercetin, rutin, coumarin, gallamine, resveratrol, scutellarin, anisidine, hesperetin, (−)-epicatechin] and other molecules (melatonin, trolox) have also been applied to function as multitarget-directed ligands. Most of these hybrids are potent inhibitors of AChE and butyrylcholinesterase and also of amyloid-beta aggregation. In addition, the antioxidant functionality, represented by coumarins, melatonin and other antioxidant molecules reduces the level of oxidative stress via ROS-scavenging mechanisms, as well as via chelation of redox-active Cu and Fe, thus suppressing the formation of ROS via the Fenton reaction. Various medicinal plants are under investigation for their ability to ameliorate symptoms of AD. The therapeutic potency of huperzine A and B, ginseng, curcumin and other compounds is manifested predominantly by the inhibitory action toward AChE, antioxidant or radical-scavenging and redox metal-chelating activity, inhibition of amyloid-beta aggregation and tau-protein hyperphosphorylation and antiinflammatory activity. Flavonoids not only function as antioxidants and metal-chelating agents, but also interact with protein kinase and lipid kinase signaling pathways, and others involving mitogen-activated protein kinase, NF-kappaB and tyrosine kinase. Among the most promising group of substances with potential activity against AD are the flavonoids, including myricetin, morin, rutin, quercetin, fisetin, kaempferol, apigenin and glycitein, which have been shown, in vitro, to possess antiamyloidogenic and fibril-destabilization activity, as well as being able to act as metal chelators and to suppressing oxidative stress. In terms of the clinical use of multifunctional hybrids, herbal drugs or flavonoids against AD, some remaining challenges are to establish the ideal dose to develop effective formulations to preserve bioavailability and to determine the stage when they should be administered. If the onset of the disease could be delayed by a decade, the number of AD victims would be significantly reduced.

Growing load and deterioration of the environment can be interpreted as a result of some external effects interventions. While the positive externalities influence the positive productional and utilizational functions of other subjects, the negative externalities influence the negative ones. Both types of external effects can act as parcial or global externalities. Linking of environmental issues to economy and finance is an important sphere

This paper deals with the application of monitoring and targeting (M&T) in the company. The main objective of this work was based on M&T study created in 2008 to assess the effectiveness of measures taken in the production distance ring. The main goal of this study was to evaluate the efficiency of measures towards electricity consumption decrease that were accepted after the study from 2008 when the process with the highest electricity consumption was identified.

The geographical information system (GIS) is a tool used generically for any computer-based capability for manipulating geographical data. The hardware and software functions of GIS include data input, data storage, data management (data manipulation, updating, changing, exchange) and data reporting (retrieval, presentation, analysis, combination, etc.). All of these actions and operations are applied to GIS as a tool that forms its database. The paper describes the types of the GIS data formats (vector, raster), database object definitions, relationships, geometric features, and the data organization structure. Some GIS applications and examples are given for better understanding of how GIS data can be used in GIS applications, with the respect to data formats, including surface elevation and slope from digital elevation model data (DEM), with the applicability in water industry.