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.
Attention was paid to the theoretical and empirical aspects of the evaluation of the thermal-hygric microclimate parameters of the working environment and their impact on the employees. The ...evaluation included questionnaire research, which involved two main areas: 1. Thermal-hygric microclimate conditions in the workplace; 2. Health problems of employees related to workplace conditions. The research was participated in by 200 employees working in manufacturing mechanical engineering organizations. The entry criterion for inclusion in the data set was the good health of the respondent, not suffering from serious health problems. The results of the evaluation showed that there is a statistically significant dependence between some of the monitored characteristics: between the age of the employee and the occurrence of monitored health problems (headache, feeling cold, spine pain), as well as between the work done and the satisfaction with the humidity of the workplace or with a feeling of dry nasal mucosa. The results of the questionnaire survey also showed a significant dependence between the type of manufacturing organization and the thermal and humidity conditions in the workplace or the occurrence of respondents' health problems. In addition, a moderately positive relationship was found between thermal-hygric microclimatic conditions and the feeling of fatigue and headaches (or feeling of cold symptoms, spinal pain, and dry nasal mucous membrane). When evaluating the questionnaire research, statistical methods were used to monitor categorical dependence.
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.
Environmentally oriented product policy is in general determined by the relationships between its aims – subjects – objects - tools. It is based on the integrated approach to the product life cycle, ...which anticipates an enormous amount of information. It has to solve the questions of the international trade as well as the rules of the International Trade Organization. New forms of preventive environmental strategies and especially Green Marketing are being introduced helping to solve environmental problems and environmental motivation of producers. Many producers face great attention of the public regarding their approach to the environment. Despite the fact that the customers buy products fairly prudently and their behaviour is markedly affected by prices, a particular part of the population prefers the products that do not burden the environment. This brings about a situation, in which the producers within their mutual competition and in relation to customers are enforced to behave responsibly.
The paper deals with meaning the term "safety" and concentrates to its sense for technical installations. It shows relations of terms reliability, resiliency, criticality, risk and safety. It ...characterizes process safety management and safety management system at technical installations. It describes methodology for ensuring the safety of technical installations. The highest quality of each object (i.e. the State, human community, technical installation etc.) is safety, so the highest priority for the object is the overall (integral) safety. This means that it is not only about partial safety such as internal, external, environmental, fire, economic, etc., but about the safety of the whole, which includes partial safety so that the condition of the whole, is optimal. Due to the systemic nature of today's world, integral safety cannot be built without regard to others. Very important is the safety of basic processes, which ensure products and services for human society. Keywords: Safety; risk management; process safety management; safety management system; methodology.
To ensure a reliable supply of electricity in a given territory, it is necessary to choose the source that is most suitable in all aspects, i.e. the availability of resources, technology, costs and ...personnel requirements. Since the requirements are incommensurable, a multi-criteria approach is chosen. Used procedure is described in detail. To ensure the development and safety of the State, each State needs raw materials, energy, transport, industry, agriculture and services to ensure the basic functions of the State. In the article, we focus on energy production, which is the basis for the extraction of raw materials, industry, transport, the operation of critical infrastructures and services that ensure the protection of the lives and health of the population, the protection of property and the protection of the environment. Keywords: Power sources; availability; risks; safety; multi-criteria approach.
The aim of the article is the measurement of media flow on a geothermal plant at a temperature of 160 degreesC, before and after gas separator during real conditions. The ultrasonic flow monitoring ...method for the measurement was used. Because of very high amount of gas in the line and high temperature of the media the F601 portable ultrasonic flow meter with extended temperature sensors was chosen. Measurement was done at three points, two of them before and one after the gas separator. The results are useful for projecting of new plants, improvements, designing the flow monitoring instrumentations of mentioned technological points or other purposes. The goal of this study is to implement the progressive non-invasive measurement method instead of inductive sensors standardly used. Keywords: Geothermal plant; Flow monitoring; Non-invasive method; Ultrasonic flow meter.
The aim of this study is to present the results of test measurements of steam flow for the development of energy balancies and the design of optimization plans, provide application model for energy ...management implementation concepts and the safety aspects. Furthermore, to demonstrate innovative technology in field of industrial measurement and theoretical analysis of such technics as a part of modern way of technology improvement. The flow measurement was performed on a low-temperature steam branch. An ultrasonic flow meter from a leading manufacturer of ultrasonic measuring technology was used for the measurement, which supplies non-invasive ultrasonic devices in addition to other process media the clamp-on technology for measuring quantitative parameters of low-temperature and high-temperature steam. Another goal is to use procedures and collected data for further research and deployment of such technology in industrial practice to increase process efficiency and operational safety. Keywords: Steam flow measurement; Ultrasonic method; Energy management; Operational safety.
This paper describes the approaches development of organizations to environmental protection through several stages from complete passivity, over so-called the reactive approach to the proactive ...principles. The passive approach relies on the power of nature to dispose of waste by own assimilative capacity, the reactive approach is based on a strategy of control and management especially in relation to the legislative measures and the proactive principle, applied in developed countries since the nineties of the twentieth century is based on the fact of prevention of pollution occurrence being cheaper and more effective than to subsequently remove it, or bear the consequences. A proactive approach focuses on eliminating problems before they have a chance to appear and a reactive approach is based on responding to events after they have happened. The difference between these two approaches is the perspective each one provides in assessing influences and their impacts. The aim of environmentally oriented management based on the proactive principles is use the special management tools and methods application are the subject of this contribution. Keywords: environment; management; protection; organisation; policy.
PDF
