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Mechanism and Effects of General Anaesthetics
Páchniková, Nina ; Groborz, Ondřej (advisor) ; Hrčka Krausová, Barbora (referee)
General anesthetics are key pharmacological agents that induce a reversible state of unconsciousness and allow surgical procedures to be performed. Despite their widespread use, the exact mechanism of action of general anesthetics remains partially unclear. This work provides a comprehensive review of historical and current theories of anesthetic function, examining general mechanisms of action and relevant target protein receptors including GABAA, glycine and NMDA receptors. It deals with the effects of specific anesthetics, namely etomidate, propofol, ketamine and isoflurane, examines their clinical effects, mechanisms of anesthetic action and interactions with various receptors. The thesis also discusses the implications of these findings, potentially informing future research directions. Key words: Anaesthetic, Pharmacology, Receptors, Review, Hypothesis
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Steroid-NMDA receptor interaction: Structure-activity and effect on mutant forms of human NMDA receptors
Hrčka Krausová, Barbora
N-methyl-D-aspartate (NMDA) receptors are glutamate-gated calcium permeable ion channels that play a key role in excitatory synaptic transmission and plasticity, and their dysfunction underlies several neuropsychiatric disorders. The overactivation of NMDA receptors by tonically increased ambient glutamate can lead to excitotoxicity, associated with various acute and chronic neurological disorders, such as ischemia, Alzheimer and Parkinson's disease, epilepsy or depression. On the opposite, NMDA receptor hypofunction is thought to be implicated in autism, schizophrenia, or intellectual disability. Recent DNA screening for neurological and psychiatric patients revealed numerous mutations in genes encoding for NMDA receptor subunits. The activity of NMDA receptors is influenced by a wide variety of allosteric modulators, including neurosteroids that could both inhibit and potentiate the activity of NMDA receptors, which makes them promising therapeutic targets. In this thesis, we describe new classes of neurosteroid analogues which possess structural modifications at carbons C3 and C17 of the steroidal core, and analogues without D-ring region (perhydrophenanthrenes). We evaluated the structure-activity relationship (SAR) for their modulatory effect on recombinant GluN1/GluN2B receptors. Our results...
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Neurosteroid modulation of ligand-gated ion-channel activity
Krausová, Barbora ; Vyklický, Ladislav (advisor) ; Moravec, Jan (referee)
The term neurosteroids refers to steroids that are synthetized in the nervous tissue from cholesterol or steroidal precursors from peripheral sources. These compounds affect the neuronal excitability by modulating the function of some ligand-gated ion channels. NMDA (N methyl D aspartate) receptors are glutamate gated ion channels involved in excitatory synaptic transmission, synaptic plasticity and excitotoxicity. GABAA ( aminobutyric acid type A) receptors mediate most of the inhibitory synaptic transmission in the mammalian brain and are targeted by many clinically important drugs. Function of NMDA and GABAA receptors can by affected by neurosteroids, both positively and negatively. The aim of this work is to summarize the current knowledge about the neurosteroid effects on the function of GABAA a NMDA receptors and suggest the physiological role and the potential therapeutic use of the neurosteroids as a regulator of some functions of the central nervous system.
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Motivy a postoje host'ov reštaurácií k prepitnému
Krausová, Barbora
Krausová, B. Motives and attitudes of restaurant guests toward gratuities. Bachelor Thesis. Brno: Mendelova univerzita v Brně, 2018. The main theme of this Bachelor´s thesis are motives of guests in Czech restaurants for gratuities and factors affecting decisions of its value, whose identification is the main goal of this thesis. The theoretical part covers problems of tourist industry, food service, service quality, consumer behaviour, satisfaction of customers and gratuities. Consequently, own analysis of the current state of food services in Czech Republic follows. The next part reveals and evaluates the most common incentives for leaving gratuities and factors affecting its value through questionnaire. The conclusion compares gained results with international research with similar case of study and formulates recommendations for providers of such services.
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Steroid - NMDA receptor interaction: Structure-activity study and effect on mutant forms of human NMDA receptors
Krausová, Barbora ; Vyklický, Ladislav (advisor) ; Anděrová, Miroslava (referee) ; Tureček, Rostislav (referee)
N-methyl-D-aspartate (NMDA) receptors are glutamate-gated calcium permeable ion channels that play a key role in excitatory synaptic transmission and plasticity, and their dysfunction underlies several neuropsychiatric disorders. The overactivation of NMDA receptors by tonically increased ambient glutamate can lead to excitotoxicity, associated with various acute and chronic neurological disorders, such as ischemia, Alzheimer and Parkinson's disease, epilepsy or depression. On the opposite, NMDA receptor hypofunction is thought to be implicated in autism, schizophrenia, or intellectual disability. Recent DNA screening for neurological and psychiatric patients revealed numerous mutations in genes encoding for NMDA receptor subunits. The activity of NMDA receptors is influenced by a wide variety of allosteric modulators, including neurosteroids that could both inhibit and potentiate the activity of NMDA receptors, which makes them promising therapeutic targets. In this thesis, we describe new classes of neurosteroid analogues which possess structural modifications at carbons C3 and C17 of the steroidal core, and analogues without D-ring region (perhydrophenanthrenes). We evaluated the structure-activity relationship (SAR) for their modulatory effect on recombinant GluN1/GluN2B receptors. Our results...
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Membrane properties of NG2 glia in CNS
Knotek, Tomáš ; Anděrová, Miroslava (advisor) ; Hrčka Krausová, Barbora (referee)
NG2 glia represent a new type of glial cells in central nervous system, which does not belong to astrocytes, oligodendrocyte or microglia. and their most frequent marker is chondroitine sulphate proteoglycan NG2. These cells keep their proliferation ability in adult brain and it is generally accepted that they can differentiate into oligodendrocytes. This thesis summarize the current knowledge about membrane properties of NG2 glia, namely expression of numerous types of ion channels and ionotropic and metabotropic receptor on their membrane. NG2 glia express outwardly and inwardly rectifying K+ channels, Ca2+ activated K+ channels and two-pore domain K+ channels. Interestingly, they also express voltage gated Na+ channels, L, T, P/Q and N type Ca2+ channels and voltage gated Cl- channels. Furthermore, nonspecific cationic channels, such as HCN and TRP, were identified in NG2 glia and they express Na+ /Ca2+ exchanger at high level. There are also ionotropic and metabotropic glutamate and GABA receptors on NG2 glia membrane, together with nicotinic and muscarinic receptors, adrenergic and glycine receptors, metabotropic and ionotropic purinergic receptors, receptors for serotonine, dopamine and histamine. Ion channels and receptors in NG2 glia play an important role in their proliferation,...
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Implementation of Family Policy in Relation to Young Adults in the Czech Republic and Sweden. Focus on Students with Children
Krausová, Barbora ; Dobiášová, Karolína (advisor) ; Kotrusová, Miriam (referee)
The objective of this thesis is to introduce the current generation of university students within the system of family policy of the Czech Republic and Sweden. The main focus is on a group of students, who got pregnant during their studies. It also points out to up to which point family policy engages in this period of their lives. The thesis' objective is also to introduce and provide with a detail view on not a particularly large group of mothers who are studying, on how they are perceived by family policies of both countries and what measures exist in the context of their situation. Both countries provide with a unique approach towards the presented situation which follows from a different evolution of family policies which are being compared. The application of tools of family policy towards student mothers in the Czech Republic and Sweden are presented on a case study. The conclusion of this thesis considers the measures which improve the situation of student mothers in Sweden and could be implemented in the Czech Republic as well.
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Study of neurosteroid effect on the NMDA subtype of glutamate receptor.
Krausová, Barbora ; Vyklický, Ladislav (advisor) ; Bendová, Zdeňka (referee)
N-methyl-D-aspartate (NMDA) receptors are glutamatergic ionotropic receptors involved in excitatory synaptic transmission, synaptic plasticity and excitotoxicity. They are heteromeric complexes of GluN1 combined with GluN2A-D and/or GluN3A-B subunits that are activated by glutamate and glycine. Many allosteric modulators can influence the activity of these receptors including neurosteroids. Pregnanolone sulfáte (3α5βS) is an endogenous neurosteroid that inhibits NMDA receptors in a use-dependent manner and has neuroprotective effect. Binding site for 3α5βS on the NMDA receptor molecule is still not indentified. The aim of my work was to contribute to the identification of the biding site by kinetic analysis of rate of response return from 3α5βS inhibition. Using the point mutation we also attempted to identify the amino acids residues that could be involved in the neurosteroid binding. In order to study the effect of 3α5βS on NMDA receptors the electropfysiological recordings on human embryonic kidney 293T cells expressing recombinant GluN1/GluN2B receptors was performed. We confirm that the effect of 3α5βS on GluN1/GluN2B receptors is voltage-independent. The results of my work indicate that steroids can reach the binding site on the NMDA receptors through the membrane rather than directly from the aqueous...
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Neurosteroid modulation of ligand-gated ion-channel activity
Krausová, Barbora ; Vyklický, Ladislav (advisor) ; Moravec, Jan (referee)
The term neurosteroids refers to steroids that are synthetized in the nervous tissue from cholesterol or steroidal precursors from peripheral sources. These compounds affect the neuronal excitability by modulating the function of some ligand-gated ion channels. NMDA (N methyl D aspartate) receptors are glutamate gated ion channels involved in excitatory synaptic transmission, synaptic plasticity and excitotoxicity. GABAA ( aminobutyric acid type A) receptors mediate most of the inhibitory synaptic transmission in the mammalian brain and are targeted by many clinically important drugs. Function of NMDA and GABAA receptors can by affected by neurosteroids, both positively and negatively. The aim of this work is to summarize the current knowledge about the neurosteroid effects on the function of GABAA a NMDA receptors and suggest the physiological role and the potential therapeutic use of the neurosteroids as a regulator of some functions of the central nervous system.
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