National Repository of Grey Literature 362 records found  1 - 10nextend  jump to record: Search took 0.00 seconds. 
Exploring the role of opioid signaling in modulation of microglial function
Mali, Akash Shivling ; Novotný, Jiří (advisor) ; Svoboda, Petr (referee) ; Machová Urdzíková, Lucia (referee)
Microglial activation is the most important component of neuroinflammation. It appears that opioids may affect microglial M1/M2 polarization in different ways depending on the type of receptor employed. In addition to opioid receptors, Toll-like receptor 4 (TLR4) of the innate immune system can also be activated by some opioid ligands and thus elicit specific cellular responses. Although opioid receptors (ORs) are known to regulate neurotransmission in various peptidergic neurons, their potential role in modulation of microglial function remains largely unknown. In this study, we investigated the effects of OR agonists, namely DAMGO, DADLE, and U-50488, on polarization and metabolic modulation of C8-B4 microglial cells. Our findings have revealed that opioids effectively suppress lipopolysaccharide (LPS)-triggered M1 polarization and promote the M2 polarization state. This was evidenced by decreased phagocytic activity, decreased production of nitric oxide (NO), diminished expression of proinflammatory cytokines such as TNF-α, IL-1β, IL-6, IL-86, and IL-12 beta p40, along with an increased migration rate and elevated expression of anti-inflammatory markers such as IL-4, IL-10, IL-13 arginase 1, and CD206 in microglia compared to cells influenced by LPS. Furthermore, we have demonstrated that...
Thoracic aorta wall pathology: diagnosis, stentgraft placement, indications, strategy and procedure technique, clinical results
Novotný, Jiří ; Krajina, Antonín (advisor) ; Chochola, Miroslav (referee) ; Roček, Miloslav (referee)
Thoracic aorta wall pathology: diagnosis, stentgraft placement, indications, strategy and procedure technique, clinical results Aim. Our single-center study was designed to assess management of thoracic aorta using a stent graft in individual types of pathology. While focused on the technical success rates and efficacy of management, the study also sought to document the incidence of intra- procedural complications and to assess the rate of sac growth and endoleak incidence. Method. A total of 86 patients with thoracic aorta disease were treated using a stent graft over a period of 12 years. They were 24 women and 62 men with a mean age 58.5 years. Late CT follow-up was performed in 75 patients, 31 (36%) were lost to follow-up, most (25) patients died. The most frequent reason (50%) for treatment included size of the aneurysmal sac, with progressive sac growth accounting for 19%. Results. Complications were rare, with most serious ones including 6 cases (7%) of hemorrhage, 3 fatal cases, with the other cases (peripheral bleeding) managed by a surgeon. Primarily intractable endoleak documented by DSA was observed in 9 treated patients (10%). The most frequent CT-documented endoleak was Type I endoleak diagnosed in 18 treated patients (20%). Spontaneous endoleak regression was demonstrated in 6...
Opioid dependence: mechanisms of development of withdrawal syndrome and its treatment
Hosenseidlová, Pavla ; Novotný, Jiří (advisor) ; Ujčíková, Hana (referee)
This work deals with opioids, opioid-induced withdrawal syndrome, and its treatment. Opioids are the most commonly used analgesics in medicine, and so far, there hasn't been a better alternative for them in most health cases. However, with long-term use, dependence can develop relatively quickly, and they have a high potential for abuse. When opioid use is discontinued, withdrawal syndrome occurs, and its symptoms resemble those of the flu, including muscle and joint pain, feeling cold and having a runny nose, nausea and vomiting, diarrhea, and tachycardia. These symptoms can be very intense and are often accompanied by psychological manifestations such as anxiety and depression. The treatment of opioid withdrawal syndrome is based on alleviating both physical and psychological symptoms. Most commonly, treatment involves using opioid agonists or antagonists with accompanying therapy for psychological manifestations. It is also important to include psychotherapy in the treatment process because the addiction in many cases stems from unresolved psychological or socio-economic issues.
Determination of opioid receptors in cerebral cortex of rats exposed to multifunctional opioid peptides
Kusová, Pavla ; Svoboda, Petr (advisor) ; Novotný, Jiří (referee)
The subject of this bachelor thesis was to study the effects of multifunctional peptides LYS739 and LYS744 on the amount of µ-, δ-, ĸ-opioid receptors (µ-OR, δ-OR, ĸ-OR) in rat cortex. Peptides were administered by the dose of 10 mg/kg for seven days. The reference group was administered a dose of 10 mg/kg morphine for the same period of the time. The effect of morphine is mainly through µ-OR. Long-term exposure to this opioid agonist results in a reduction in the function and quantity of these receptors in the development of tolerance and dependence. Multifunctional opioid peptides have begun to be investigated for their therapeutic potential to reduce adverse effects and increase efficacy. Their potential lies in their ability to interact with multiple opioid receptors. Peptides LYS739 and LYS744 act as agonists of µ-OR, δ-OR and simultaneously as antagonists of ĸ-OR. The amount of opioid receptors was determined by SDS-PAGE followed by Western blot. The results were compared with a control group that was administered by saline and a reference group that was administered by morphine. There was almost no change in the δ-OR, ĸ-OR receptors. In the case of µ-OR, there was a decrease in morphine and LYS739, but this change was not assessed as statistically significant.
The effect of long-term morphine and its withdrawal on selected signaling proteins in rat heart
Ilková, Karolina ; Novotný, Jiří (advisor) ; Černá, Věra (referee)
Morphine is considered the gold standard among analgesics in the treatment of severe pain due to its effects mediated by μ-opioid receptors. However, it also produces various side effects and poses a high risk of developing tolerance and dependence. The aim of this bachelor thesis is to contribute to the elucidation of the action of morphine at the molecular level in cardiac muscle. Changes of protein levels in key signaling molecules in the signaling cascade induced by morphine administration with increasing doses and subsequent abstinence for 24 hours, 1 month and 3 months were investigated. Specifically, these were adenosine A2b receptor, β2-adrenergic receptor, κ-opioid receptor, G protein subunits, GRK5 kinase, and β-arrestin 2. Data of changes in expression were obtained from cardiac tissue homogenates (left ventricle) by Western blot followed by immunodetection, captured on light-sensitive photofilms, and statistically evaluated by ANOVA. Morphine administration did not lead to statistically significant changes in G protein subunits, β- arrestin 2, GRK5 kinase, adenosine A2b receptor, β2-adrenergic receptor, or κ-opioid receptor in rat heart. Therefore in order to develop better and safer analgesics, there is a high necessity of understanding the underlying molecular mechanisms of morphine...
Role of β-arrestin in μ-opioid and TRPV1 receptor signalling
Nagy Marková, Vendula ; Novotný, Jiří (advisor) ; Blahoš, Jaroslav (referee) ; Roubalová, Lenka (referee)
β-Arrestin belongs to the protein family which has a huge impact not only on GPCR signaling, but its role exceeds the function of the membrane channel, its own signaling cascade, or as a scaffold protein, etc. Here we aimed to study β-arrestin roles on the MOR behaviour in the plasma membrane or -opioid receptor (MOR) signaling and effect on adenylyl cyclase (AC) function using the siRNA to decrease the expression of β-arrestin isoforms. Furthermore, we focused on investigating the role of β-arrestin on the crosstalk between MOR and TRPV1 channels, which are important parts of pain transduction. For this purpose, we used HEK293 cells that stably expressed MOR-YFP or transiently transfected with TRPV1-CFP. We observed that both β-arrestin isoforms have an effect on the lateral mobility of MOR in the plasma membrane and the silencing of one or another β-arrestin isoforms abolishes the effect of MOR agonists to affect its diffusion in the plasma membrane. Interestingly, silencing of β-arrestin1 diminish the internalization of MOR induced by the endogenous agonist endomorphin-2. On the other hand, silencing of β-arrestin2 did not abolish the endomorphin-2 induced MOR internalization. Moreover, both isoforms exhibit a distinct impact on the inhibition of AC induced by the agonists of MOR....
Designing and programming wireless lens control system
This work focuses on designing and programming a product, that wirelessly controls the focus ring of a camera lens. The product is based on an Arduino nano programmable circuit board incorporating an ATmega328P microcontroller, that is used for all calculations, stores the whole code on a flash memory, controlling the inputs and outputs of an electronic components specifically a potentiometer, a buttons, a step motor, a motor driver and a wireless modules. The final product consists of two smaller devices, the transmitter, which is held by the user for sending information and the receiver controlling the motor. Both devices are powered by USB power banks. Programming and debugging take place in Arduino IDE. Designing and modelling parts e.g. spur gears and the case uses Blender. Final outcome aims to make cheaper, but equally efficient product as the commercial solution for this product.
On relevant deformations in Open String Field Theory
Scheinpflug, Jaroslav ; Schnabl, Martin (advisor) ; Novotný, Jiří (referee)
String field theory takes string perturbation theory off-shell and since the different vacua of string theory are described by conformal field theories, it is tempting to use string field theory to describe conformal perturbation theory. We use open string field theory to reproduce the known leading order results of boundary conformal perturbation theory and we also perform the next-to-leading order calculation of the boundary degeneracy g for a generic theory. This is achieved by finding perturbative solutions to the classical equations of motion of open string field theory corresponding to weakly relevant deformations. The observables of conformal perturbation theory are then given by calculating the on-shell action or by invoking the Kudrna-Maccaferri-Schnabl correspondence. We also lay the groundwork for the investigation of the shift in the boundary spectrum. This work is largely based on the collaboration with Martin Schnabl [1].
Psilocybin: the mechanism of action and therapeutic potential
Mintálová, Tímea ; Novotný, Jiří (advisor) ; Vejmola, Čestmír (referee)
Psilocybin is a psychoactive molecule derived from tryptamine precursors that is present in some mushrooms, especially those belonging to the Psilocybe genus. Its pharmacologically active metabolite, produced by dephosphorylation, is psilocin, which can cross the blood-brain barrier. It is believed that the psychedelic effects of psilocin result from its partial agonistic activities on 5-HT2A receptors, the main receptor subtype among serotonin G-protein-coupled receptors (GPCRs). Psilocin also binds to a number of other subtypes of these receptors, but the effects it has on these receptors have not been fully explored yet. Psilocybin has been studied for its potential use in treating anxiety, depression, and disorders caused by addictive substances when administered in concentrations sufficient to produce psychedelic effects. The pharmacological potential of psilocybin is without the risks of potential addiction or overdose compared to other psychoactive drugs such as cocaine, alcohol, methamphetamine, and others. Due to the increasing worldwide trend of addiction, overdose, and suicidal deaths, it is necessary to seek new therapeutic alternatives. However, it is also necessary to assess various contraindications that may limit the possibility of using psilocybin as a pharmacological therapy....
The role of RNA demethylase FTO in differentiation, regulation of energy metabolism and sensitivity to streptozotocin of neuronal and glial cell models
Čočková, Zuzana ; Novotný, Jiří (advisor) ; Horák, Martin (referee) ; Balík, Aleš (referee)
Fat mass and obesity associated (FTO) demethylase is responsible for erasure of the most abundant epitranscriptomic mark in eukaryotic mRNA, the N6-methyladenosine (m6A) residue. Together with other m6A erasers, writers (methyltransferases) and readers it forms an m6A regulatory pathway that controls the amount, location and biological effect of m6A. The dynamic regulation of the brain's m6A methylome during neurodevelopment is essential for maintaining cerebral functions. In addition, preclinical research suggests that the m6A regulatory pathway regulates energy balance in a tissue- and cell type-specific manner. The FTO gene has been associated with lifelong risks of obesity and metabolic syndrome as well as regulation of total body energy intake and expenditure. However, little is understood about the function of the m6A pathway in control of brain energy metabolism. That is of interest in pursuit of understanding Alzheimer's disease, as this illness is characterized by profound disruptions in cerebral energy metabolism and mounting evidence suggests that disrupted brain bioenergetics may play a role in the disease's early genesis, before the appearance of clinical symptoms. In the present thesis we aimed to investigate the role of FTO in models of two brain cell types, neurons and astrocytes....

National Repository of Grey Literature : 362 records found   1 - 10nextend  jump to record:
See also: similar author names
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