English abstract Diabetes mellitus (DM) is the best known endocrine disease of the pancreas where the incidence of the affected individuals is increasing rapidly worldwide. It is caused by defects in both the pancreatic islets and in the pancreas to produce enough insulin resulting in impaired glucose homeostasis leading to higher than normal glucose levels in the blood (hyperglycaemia) which is considered to be the hallmark of diabetes. Consequently the main aim of diabetes management is to monitor the glycaemic status. Diabetes mellitus can be subdivided into two classes, type 1 diabetes mellitus (T1DM) which is also known as insulin- dependent diabetes mellitus and type 2 diabetes mellitus (T2DM) which is known as non- insulin-dependent diabetes mellitus. Management of either type of DM requires a number of lifestyle modifications such as increased exercise and decreased weight with the intention of improving metabolic control and enhancing the quality of life. Unfortunately, the majority of patients will eventually require administration of antidiabetic drugs. The present study was performed with the intention of reviewing the currently available scientific literature about both types of DM and discuss the current and novel approaches of treatment, thus giving more emphasis on the novel advances. For...

N-methyl-D-aspartate receptors (NMDARs) are heterotetramers containing two obligatory glycine-binding (GluN1) and two glutamate/glycine-binding (GluN2/3) subunits. These receptors mediate excitatory synaptic transmission in the central nervous system and play a key role in high order neuronal processes as a learning and formation of memory. It has been shown that dysregulation of NMDARs is involved in the pathophysiology of neurological and psychiatric disorders. Each receptor is composed of four protomers exhibiting a conserved domain organization. The most distal part to the cell membrane is the amino-terminal domain that is linked to the ligand binding domain (LBD), which is connected to the pore-forming transmembrane domain (TMD) communicating with the intracellular carboxy-terminal domain. LBD and TMD are connected via three polypeptide chains - linkers. Channel opening is the key step in the NMDAR gating that allows the flux of ions across the membrane. The energy of agonist binding-evoked conformational changes is transferred via linkers to M3 helices forming an ion channel. The rearrangement of M3 helices in activated receptor makes the central cavity of the channel accessible. The details of energy transfer are not yet fully characterized, although accurate knowledge of the receptor gating...

This thesis deals with a medical and social view of taking healing hemp (cannabis). It is a theoretical thesis elaborated based on the analysis of the available Czech and foreign information sources and professional publications. The thesis target is to map the issue of taking healing hemp by means of the information from the available foreign and Czech literature. The thesis focuses on the most important issues dealt with by the professional as well as lay public and on the development of the solution of this issue. I was captured by this issue after my internship in Belgium, where I had the opportunity to travel through neighbouring Netherlands and to get to know, from the viewpoint of a foreigner, the opinions and access of the inhabitants to the hemp as healing and relaxing mean. The first chapter deals with using the healing hemp in the historical context. Hemp represents one of the oldest crops and for this reason the history of hemp in the period of antiquity, Middle Ages and modern times is described. The following chapter focuses on the individual substances contained in hemp. In this chapter, the endo-cannabinoid system and three kinds of substances contained in hemp strains are analysed canabinoids (THC), canabidiols (CBD), canabinols (CBN). The chapter presents the profile of one of the most important personalities associated with hemp, professor Raphael Mechoulam, the main icon and discoverer of THC. The chapter three devotes to toxicology and addiction when taking hemp, which occurs quite rarely among users of hemp drugs. In this chapter, influence of hemp on the memory of user is treated, as well as the influence of hemp on the occurrence of lungs diseases discussed constantly in connection with smoking and in the last part of this chapter, the addiction and influence of hemp on users psyche is analysed. The following chapter is devoted to the issue of the drug policy, especially defining the status of healing hemp in the law, research of healing hemp and legalization of hemp in the Czech Republic. This chapter is devoted in detail to the legalization of hemp in the world, especially in the states like California, Israel, Canada and Netherlands where the hemp was legalized for healing purposes many years ago. The present science brings a wide spectrum of clinical research examining the effects of hemp during the treatment of many diseases. For this reason, the chapter dealing with hemp in connection with medicine is present in the thesis. Six areas were chosen from individual medicine branches on which this chapter is focused. The reader learns about the healing effects of hemp in the area of oncological diseases, psychiatric diseases, palliation of pain, dermatological diseases, multiple sclerosis and HIV/AIDS. In the last chapter, the opinions and experiences of the professional public in connection with hemp are described. This part deals with the contribution of the newest knowledge presented at the Prague conference about healing hemp. In this part of thesis, also the international hemp Cannafest Trade Fair is mentioned held in 2015 in Prague. It follows clearly from the thesis that the health and social issues connected with healing hemp is the topic of extensive and long-lasting discussions at present. In the area of the lay public, there is interest in this form of medical treatment which is supported quite a lot. The thesis may be used as information source by medical/paramedical and social employees and organizations supporting the legal use of healing hemp. It could represent the base of a professional article for the journal dealing with this topic as e.g. professional journals "Legalization" or "Health." Last but not least, the thesis should serve as complex of information for the persons who decided to take the hemp or consider this possibility.

The diploma thesis deals with the issue of health literacy of seniors in the field of pharmacology. The aim of the work was to find out, which skills and abilities seniors have, to understand, search and use information, services, and tools related to pharmacology. Thanks to these social and cognitive skills, seniors can have greater control over their health, they can make good decisions about their health condition, and they can maintain and support their health in general. The second aim of this thesis was to find out what problems the seniors encounter in the daily use of medicaments and what aspects make them the most difficult. With today's overusing drugs, seniors face more than one problem and it is affecting their quality of life and whole drug therapy. To achieve my goals, I have used quantitative research, using questionnaires. The examined sample was male and female from the age of 65 and the total number of respondents was 120. I set 2 goals with eight related hypotheses. Based on the gained results, out of the eight hypotheses, two of them were accepted and six of them were rejected. Based on the gained information from the research, in collaboration with graphic designer Dominika Pýchová, I created a stylized illustration (Annex 2), which could be introduced in the packaging to simplify pharmacy's using by seniors and simplify the information from information flyers. The reason, why seniors don't read the information flyers is the fact, that printed letters are too small and not readable. I was present while filling out the questionnaires and that is why I found out, that seniors would welcome better and uniform drug list which would make them easier to use. That's why I redrew the American version of the drug list, which is listed in (Annex 3). Overall research shows that half of the seniors are using more than 5 drugs, they have bigger problem of knowing the effects of drugs than knowing their names. Almost nobody knows the side effects of the drugs, as well as a clinical pharmacist who would facilitate pharmacotherapy in many cases. Practitioners do not check their patients' medication, and in many cases, when hospitalized, practitioners find out that the patient is taking unnecessary medication or even those that have not been prescribed for a long time. As long as the seniors do not improve their knowledge with help from practitioner and nurse, or by introducing of drug list's regular checks, seniors will be in alarming danger and their health literacy will not improve but it will be further reduced.

Spatial navigation is essential for survival not only in mammals. Neural and neuropharmacological changes of learning and memory in humans and rats could be measured through their behavior and responses to stimuli. In focus of experimental models of cognitive deficits, the Morris water maze (MWM) represents a clasiccal test of exact allothetic representation, i.e. the cognitive map. Another important test of spatial navigation is the active place avoidance, or Carousel maze (also AAPA, Active Allothetic Place Avoidance), that can be used to test the ability of cognitive coordination, thus the ability to distinguish relevant stimuli from irrelevant. There are analogous tasks for testing cognitive abilities in humans for both tests (e.g. Blue Velvet Arena for MWM, virtual reality simulations on PC for AAPA, etc.). Aim of the present study is to compare the sensitivity of outbred Long-Evans and Wistar strains of rats from the institutional breeding to the acute administration of scopolamine, the antagonist of central muscarinic acetylcholine receptors, at doses 0.8 mg/kg; 1.5 mg/kg and 3.0 mg/kg. The results show that the Wistar strain is more influenced by cholinergic blockade than Long-Evans strain in both AAPA and the MWM. Furthermore, it appears that the control rat strain Long-Evans have better...

In preclinical research on Alzheimer's disease pharmacotherapy, attention is paid to multipotent compounds, enabling intensification of the effect by targeting multiple pathophysiological mechanisms. The aim of the thesis was to assess the effect of multipotent compounds and combination therapy in models of cognitive deficit in the rat. The mechanism of action of the tested compounds was modulation of neurotransmitter systems. The aim of the first part of the study was to compare the effect of experimental monotherapy and combination therapy with an N-methyl-D-aspartate (NMDA) receptor antagonist and a γ-aminobutyric acid type A (GABAA) receptor positive modulator in the trimethyltin-induced model. Superiority of the combination therapy was proven by histological analysis of hippocampal neurodegeneration; however, it did not reach statistical significance in the cognitive test. The other part of the thesis focused on multipotent tacrine derivatives. We demonstrated a positive effect of 6- chlorotacrine-6-nitrobenzothiazole hybrid, as well as 6-chlorotacrine-L-tryptophan hybrid, acting as acetylcholinesterase inhibitors, in the scopolamine-induced model of cognitive deficit. Besides, we demonstrated a low risk of serious side effects of other tacrine derivatives acting as NMDA receptor antagonists....