|
|
Pharmacological and metabolic influence on liver mitochondrial functions
Sobotka, Ondřej ; Červinková, Zuzana (advisor) ; Kuncová, Jitka (referee) ; Žurmanová, Jitka (referee)
Liver mitochondria play a crucial role in intermediary metabolism and main metabolic pathways. We evaluated the pharmacological effect on liver mitochondria in vitro using two novel anticancer drugs: 3-bromopyruvate and α-tocopheryl succinate. Metabolic influence on liver mitochondria was performed in vivo by high fat and high cholesterol diet. Toxicity of both drugs was evaluated in cell cultures of hepatocytes isolated from rat and mouse liver. The effect of anticancer drugs on liver mitochondrial functions in vitro was studied on suspensions of isolated liver mitochondria, tissue homogenate and permeabilized hepatocytes. Mitochondrial respiration was measured using high-resolution respirometry. 3-bromopyruvate caused morphological and functional damage of primary rat and mouse hepatocytes in cell cultures; this toxic effect was accompanied by an increase of reactive oxygen species production and mitochondrial dysfunction. 3-bromopyruvate decreased the oxygen consumption of mitochondria energized by substrates for complex I and complex II. α-Tocopheryl succinate caused a decrease of succinate-dependent respiration in all experimental models both in coupled and in uncoupled states. The most pronounced effect of α-tocopheryl succinate was apparent in isolated mitochondria and the least pronounced...
|
|
|
Some aspects of molecular mechanisms of xenobiotics' hepatotoxicity and hepatoprotection : Modulatory roles of natural polyphenols
Lekic, Nataša ; Farghali, Hassan (advisor) ; Kršiak, Miloslav (referee) ; Brůha, Radan (referee)
Background & Aims: Oxidative stress and apoptosis are proposed mechanisms of cellular injury in studies of xenobiotic hepatotoxicity. The aim of this work is to find early signal markers of drug-induced injury of the liver by focusing on select antioxidant/oxidant and apoptotic genes. As well, to address the relationship between conventional liver dysfunction markers and the measured mRNA and protein expressions in the D-galactosamine/lipopolysaccharide and tert-butylhydroperoxide hepatotoxicity models. Furthermore, potential hepatoprotective capabilities of antioxidant polyphenols quercetin and curcumin were evaluated in relation to its modulation of the oxidative stress and apoptotic parameters in the given xenobiotic hepatotoxicity models. Methods: Biochemical markers testing the hepatic function included aminotransferases (ALT, AST) and bilirubin. Measurements of TBARS and conjugated dienes were used to assess lipoperoxidation. Plasma levels of catalase and reduced glutathione were used as indicators of the oxidative status of the cell. Real time PCR was used to analyse the mRNA expressions of the inducible nitric oxide synthase (NOS-2), heme oxygenase-1 (HO-1), superoxide dismutase (SOD-1), glutathione peroxidase (Gpx-1), caspase 3 (Casp3), BH3 interacting domain death agonist (Bid) and Bcl-2...
|
|
|
Organoids - the phenomenon of complex organ-like structures cultivation in vitro
Vilímková, Veronika ; Janečková, Lucie (advisor) ; Rothová, Olga (referee)
Pluripotent embryonal stem cells (ESCs) are unique for their ability to proliferate and differentiate into almost all cell types. In the presence of appropriate stimuli, they are able to initiate morphogenesis in vitro. Stem cells are able to differentiate into specific cell lines of a given tissue and to arrange three- dimensional (3D) structures. These so-called organoids are formed in a self-organizing process that mimics normal ESCs development. Organ development is a complex process that requires temporally and spatially ordered regulatory signals. 3D organization of these structures allows important cell-cell interactions. Organoid cultures are thus the area of a huge potential. Organoids are accessible to all standard experimental manipulations. They are therefore an ideal tool for the research of stem cells, signaling pathways, organogenesis and disease modeling. Finally, they may open up new avenues for regenerative medicine and gene therapy. Powered by TCPDF (www.tcpdf.org)
|
|
|
Case Study of Physiotherapy Treatment of a Patient after ALPPS for leiomyosarcoma.
Čemusová, Kateřina ; Opatrná Novotná, Irena (advisor) ; Charvát, Robert (referee)
Author: Kateřina Čemusová Title: A case study of physiotherapy treatment of a patient after ALPPS for leiomyosarcoma. Aims: This thesis aims to record physiotherapy care for the patient after undergoing ALPPS treatment for leiomyosarcoma, determination, management and recording of individual therapeutic units, and evaluation of their effect. Methods: The thesis consist of a theoretical and practical part. The theoretical part consist of general information about the composition and physiology of the liver. Leiomyosarcoma and other liver diseases are also described. Lastly, the ALPPS method is mentioned. All information is cited from academic literature and other professional sources. The practical part contains a case report of a patient, who has undergone ALPPS treatment for leiomyosarcoma. It also contains the record of individual therapies, that have been performed based on a kinesiological analysis. The analysis has been done as a part of a physiotherapy intership at the Institute of clinical and experimental medicine in Prague from 18th January to 12th February 2021. Results: The treatment and the effect of therapeutic care were significantly slowed down due to the division of the surgery into two stages. In general, the dysbalances of muscle strength and hypertonia have been corrected. The...
|
|
|
Expression of enzymes of kynurenine and methoxyindole pathway in the rat pineal gland, liver and heart in circadian profile and after lipopolysacharide administration
Hrubcová, Leona ; Bendová, Zdeňka (advisor) ; Svobodová, Irena (referee)
Tryptophanis anaminoacidwhichhasmanyfunctionsinthebody. Besidesitsparticipationin theproductionofproteins,itactsasasubstrateforthekynurenineandmethoxyindolemetabolic pathways. The kynurenine pathway ends with the production of nikotinamid e adenin dinukleotide ( NAD + ) ,whichisneededfortheproductionofcellularenergy. Thus,withincreased energy demand during immune system activation, the activity of the kynurenine pathway is increased. Dueto increasedactivity,itproduces more immunoactiveandneuroactivemetab olites suchaskynurenicacidandquinolinicacid.Thesemetabolitesareinvolvedinmanyprocessesin the body and affect the pathology of many diseases. Studies show that regulation of these metabolites could be a key innovation in the treatment of cance r, cardiovascular or neurodegenerative diseases. The methoxyindole pathway is another important tryptophan processingpathway.Itsbest - knownmetabolitesareserotonin,whichactsasaneurotransmitter, andmelatonin,ahormonewithimmunomodulatoryeffect sregulatedby thecircadianclock . This workdeals with thecircadian rhythmicityofenzymeexpressionofthesetwo metabolic pathways.Italsodescribestheeffectofsystemicadministrationoflipopolysaccharideendotoxin ontheexpressionofgenesoft heseenzymes.OurexperimentsusedWistarratsat30daysofage. The lipopolysaccharide was administered...
|
|
|
Effect of selected food supplements on metabolism of food-born carcinogens
Fousová, Petra
The consumption of dietary supplements such as flavonoids may reduce risk of many civilization diseases. Flavonoids are able to modulate the activity of cytochromes P450 (CYPs), xenobiotic-metabolising phase I enzymes of biotransformation that are involved in the activation and detoxification of food-derived carcinogens. Inhibition of CYP activities by flavonoids has been extensively studied because of their potential use as agents blocking the initiation stage of carcinogenesis. On the other hand, flavonoids have been shown to enhance the activation of carcinogens and/or influence their metabolism via induction of specific CYPs. In the first part of this study, flavonoids dihydromyricetin and α-napthoflavone were explored for their possible effects on CYP1A1 expression and activity when administered in combination with carcinogen benzo[a]pyrene (BaP). For this purpose, liver, small intestine and colon microsomal fractions were isolated from treated rats and induction of CYP1A1 was evaluated by immunodetection and EROD activity measurements. In liver and small intestine, all combinations of BaP and flavonoids led to strong induction of CYP1A1 expression. Moreover, the CYP1A1 protein levels were almost identical to levels observed when the rats were treated with BaP alone. However, in comparison...
|
|
|
Changes of internal organs after percutaneous exposure to sulfur mustard
Šulová, Veronika ; Červený, Lukáš (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Veronika Šulová Supervisor: doc. PharmDr. Lukáš Červený, Ph.D. External supervisor: pplk. doc. MUDr. Jaroslav Pejchal, Ph.D. et Ph.D. Title of diploma thesis: Changes of internal organs after percutaneous exposure to sulfur mustard Sulfur mustard is a chemical warfare agent belonging to the group of blistering agents. The theoretical section of the thesis is mainly focused on the description of acute toxic effects, the mechanism of action, and deals with the current possibilities of poisoning therapy. The experimental section is focused on monitoring the effect of sulfur mustard poisoning in the liver, lung, and kidney of female C57BL/6J mice after the percutaneous administration. This work aimed to evaluate markers of oxidative stress and histopathological changes of the selected organs at 3, 5, and 7 days after the poisoning. Ferric reducing antioxidant power (FRAP) and thiobarbituric acid reactive substances (TBARS) methods were used to determine markers of oxidative stress. Histopathological changes were evaluated microscopically using the hematoxylin-eosin staining method. The airness of the lung parenchyma was also assessed by computer image analysis. First, the LD50 of sulfur mustard was...
|
|
|
The case study of physiotherapy treatment of a patient after liver transplantation.
Švejdová, Jana ; Stupková, Michaela (advisor) ; Charvát, Robert (referee)
Title: The case study of physiotherapy treatment of a patient after liver transplantation. Author: Jana Švejdová Head of the thesis: Mgr. Michaela Stupková Objectives: The aim of this bachelor thesis is to summarize the facts about liver transplantation including an example of physiotherapeutic treatment on a specific patient after liver transplantation. The thesis is written from a physiotherapeutical point of view. Methods: The bachelor thesis consists of two parts - theoretical part and special part. The theoretical part contains information about anatomy, physiology and pathology of the liver, including liver diseases, description of the transplantation process and physiotherapeutic techniques used after the surgery. All of this information was obtained from scientific literature. The special part of this thesis describes the case study of a specific patient after undergoing liver transplantation including a description of physiotherapeutic care, examinations and therapeutic units. This part was created during my practice in the Institute of Clinical and Experimental Medicine in Prague between 6th and 31st January 2019. Results: The main improvement was in muscle strenght and overal physical condition being noticeable mostly in the gait ability and activities of daily living. Keywords: liver,...
|
|
|
Case Study of Physiotherapy Treatment of a Patient after Liver transplantation
Šťastná, Tereza ; Neuwirthová, Svatava (advisor) ; Charvát, Robert (referee)
Author: Tereza Šťastná Title: Case study of physiotherapy treatment of a patient after liver transplantation Aims: The aim of this bachelor's thesis is to process theoretical knowledge about liver, liver transplantation and to perform a case report of a patient who underwent transplantation. Methods: This thesis is created on the basis of continuous monthly practise at the Institute of clinical and experimental medicine at the department of KARIP, which took place in the period from 6th to 31st January 2020. Thesis is divited on theoretical and practical part. In theoretical part are compiled informations about anatomy and physiology of liver, than about liver diseases and liver transplantation. In the end of this part are informations about physiotherapic care after liver transplantation. Practical part conteins case study of physiotherapy treatment of patient after liver transplantation and daily records of individual therapies. The bachelor thesis is written from the point of view of a physiotherapist. Results: The patient was in coma almost whole time of therapies, that fact greatly affects their process. The greatest success was increase of muscle strength and deepening of tidal volume during therapies. In the last days of practice, the patient's health deteriorated rapidly and unfortunately...
|
|
|
The case study of physiotherapy treatment of a patient after liver transplantation
Sosnovcová, Veronika ; Vomáčková, Helena (advisor) ; Charvát, Robert (referee)
Author: Veronika Sosnovcová Title: The case study of physiotherapy treatment of a patient after liver transplantation Objectives: The main aim of this bachelor thesis is to elaborate theoretical knowledge of liver transplantation and to introduce the case study of physiotherapeutic treatment of the patient who has undergone a liver transplant. Methods: The bachelor thesis consists of two parts. The first part is the theoretical part, which summarizes basic information about anatomy, physiology and patology of the liver. The next chapter is about one of the main treatment options in advanced liver disease, what is the liver transplantation. Physiotherapeutic procedures that can improve patient's condition are mentioned in the last chapter of the theoretical part. The special part describes the case study of the patient after liver transplantation. It also includes the record of individual therapies, which was applied during the practice in IKEM in January 2020. Results: The patient improved after the therapies. The most important progress was that patient could walk unassisted along the corridor and even up and down the stairs. The patient became completely independent and was discharged home. Keywords: liver, transplantation, cirrhosis of the liver, physiotherapy
|
guest ::
