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Modulace exprese alfa-synukleinu pomocí působení 5-S-cysteinyldopaminu na buňky lidského neuroblastonu SH-SY5Y: možná úloha katecholthioetherů při neurodegeneraci
Hrabáková, Rita ; Štaud, František (advisor) ; Mladěnka, Přemysl (referee)
-Synuclein is a presynaptic protein which has been demonstrated to be involved in PD etiopathogenesis.It can regulate DA homeostasis by inhibition of TH activity, by regulation of the DAT activity and finally by potential role in vesicular storage. - Synuclein is a natively unfolded protein, which can undergo overexpression and aggregation due to toxic insults or oxidative stress. The aggregation of α-synuclein leads to a loss of function, which in PD neurons may determine a dysregulation of the DA pathways with subsequent excess of cytosolic DA, that can enhance the neurotoxic effect of α-synuclein aggregates. In recent years, a catecholthioether metabolite of DA, 5-S-cysteinyl-dopamine, has been identified in certain dopaminergic regions of the brain, notably the Substantia nigra. Cys-DA seems to have a possible significance as an index of oxidative stress in aging and in neurodegenerative processes and it was recently hypothesized that this substance or its metabolites may be the endogenous neurotoxins responsible for neurodegeneration in PD. Hence, the aim of this experimental work was to determine whether Cys-DA is able to cause overexpression of -synuclein both at transcriptional and translational levels in a cellular model of PD, the human neuroblastoma dopaminergic cell line SH-SY5Y....
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Treatment of arterial hypertension
Mlčochová, Michaela ; Tilšer, Ivan (advisor) ; Mladěnka, Přemysl (referee)
Topic: Therapy of arterial hypertension Author: Michaela Mlčochová Arterial hypertension is one of the most common diseases of cardiovascular system. Long-lasting high blood pressure is associated with development of organ damage and adverse prognosis. Accurate diagnosis and precision treatment decrease markedly the risk of hypertensive and atherosclerotic complications such as coronary heart disease, cerebrovascular events, heart failure and end-stage renal disease. Most of the hypertensive patients require pharmacological treatment to attain recommended levels of blood pressure. Lifestyle modification shoud be a part of the treatment of all hypertensive patients. Present pharmacotherapy offers a range of drug classes (ACE inhibitors, calcium channel blockers, diuretics, ARBs, beta-blockers), which demonstrated favourable influence on cardiovascular morbidity and mortality. They are suitable for montherapy as well as combination therapy. Recently, the combination therapy is emphasizes because of great number of hypertensive patients have an inadequate blood pressure control.
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Pharmacological screening of substances with iron chelating activity
Havránková, Lenka ; Jahodář, Luděk (referee) ; Mladěnka, Přemysl (advisor)
v anličtině Iron is an important element involved in many vital processes. Its defficiency stops of cell growth and can lead even to a cell death. On the other hand excess of iron is dangerous for organism because of its catalytic participation on free radical formation. Therefore the amount of iron in the organism has to be meticulously regulated. Iron chelators are used when the organism is iron-overloaded. Flavonoids are vegetal polyphenols derivated from a heterocyclic compounds named flavan. They are an important components of the antioxidant system and are able to react with free radicals and to chelate some metal ions. In this study, nine flavonoids (apigenin, kaempferol, quercetin, rutin, hesperetin, hesperidin, naringenin, naringin and catechin) were tested for their chelation activity and compared with clinically used iron chelator desferrioxamine. Suitable experimental conditions with use of ferrozine as an ferrous ion indicator were found for spectophotometric assesment of iron-chelation efficiency. For assessment of the total chelation, hydroxylamine was used as the reductant. Chelator with the highest chelation activity was clinically used desferrioxamine, from tested flavanoids was the most effective apigenin. Practically ineffective flavanoids were catechin hesperetin, hesperidin,...
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Zhodnocení antioxidační aktivity lipofilních esterů hydroxytyrosylu
Jarkovská, Stanislava ; Martin, Jan (referee) ; Mladěnka, Přemysl (advisor)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Stanislava Jarkovská Supervisors: Prof. Sandra Incerpi, Dr. Přemysl Mladěnka Title of diploma thesis: Evaluation of antioxidant activity of hydroxytyrosyl lipophilic esters Scavengers of reactive oxygen and nitrogen species (RONS) or shortly antioxidants could have beneficial effects in diseases associated with oxidative stress. In addition, antioxidants are widely used today for stabilization of fats and oils in food matrices. Hydroxytyrosol, the main phenolic compound of olive oil, possesses strong antioxidant activity. Due to its highly polar nature it is less soluble in lipophilic environment that limits its use as antioxidant in foods and in prevention/treatment of diseases. The aim of this thesis was to compare scavenging potential of parent compound hydroxytyrosol to its lipophilic esters with different side chain length. Antioxidant capacity of these esters that were synthetized in the Laboratory of Chemistry, Department of Mechanical and Industrial Engineering in university Roma Tre, were examinated in vitro in 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid diammonium salt (ABTS) radical scavenging assay and in L6-myoblasts in culture dichloroflourescein (DCF)...
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Interrelationship of basic biochemical parameters in patients of type II diabetes mellitus
Mazurová, Monika ; Boušová, Iva (referee) ; Mladěnka, Přemysl (advisor)
Diabetes mellitus 2nd tipe is heavy and very frequent civilizing disease in our population. The disease is characterized by hyperglycemia and other metabolism abnormalities are prezent. Assesment of glycemia in plasma (serum) is used for a diagnostics of the disease. Indicator of long- term compensation of diabetes is glycosylated haemoglobin. There were monitored possible dependensies between biochemical indicators in this work that are assesmented to diabetic patiens commonly. The dates were analyse from 54 diabetic patiens between the ages of 40 to 82 who visit a diabetic clinic periodically. The samples were analyzed by Cobas Integra 800 analyzer by Roche (Germany). Glucose in serum and in urine was analyzed by enzymatic metod with hexocinase and glycosylated haemoglobin was analyzed by imunochemical metod based on thurbidimetric inhibition in haemolysed blood. Paerson's correlative coefficient was used for appreciation of dependencies between variables. The highest correlative coefficient was found between glucose measuring in morning urine and glucosic losses by urine for 24 hours. Statistically important correlation were also found between glucose in serum and in urine or glucosic losses by urine for 24 hours and between glucose in serum and glycosylated haemoglobin. Because of relatively...
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Viral hepatitides and their pharmacotherapy
Klímková, Martina ; Vokřál, Ivan (referee) ; Mladěnka, Přemysl (advisor)
15. Abstract Viral hepatitis belongs to the most common infectious diseases in the world by this time. Typical areas of their appearance are countries of South America, South Asia and Africa. They are transmitted parenterally (hepatitis B, C, D) or via the faecal-oral route (hepatitis A, E). Infection starts the immune reaction with production of antibodies that often serve in confirmation of the definitive diagnose. The clinical manifestation of viral hepatitis involves gastrointestinal discomfort, jaundice and actually liver failure and death if the hepatitis is complicated or untreated. Hepatitis A and hepatitis E don not become chronic and patients do not have any health consequences after recovery. Chronic forms of hepatitis B, C, and D cause long-lasting complications. There is no need to use antiviral drugs in the therapy of hepatitis A and E, the symptomatological therapy is sufficient. The other types of hepatitis demand an antiviral therapy. The basic of this therapy are interferon and synthetic nucleoside analogues. Interferons start an appropriate immune reaction and destroy infected hepatocytes and synthetic antivirotics inhibit synthesis of viral nucleic acid. In the treatment of hepatitis B is used pegylated interferon α, ordinarily in combination with nucleoside analogues (lamivudin,...
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Effect of lactoferrin on macroscopical and histological features in different tissues in rats. II. Liver and kidneys.
Škrle, Jan ; Semecký, Vladimír (advisor) ; Mladěnka, Přemysl (referee)
Lactoferin is an 80-kDa iron-binding glykoprotein. It shares a high degree of homology at amino acid sequence level and also the three dimensional conformation level with transferin. Both proteins are classified in the family of iron-binding glykoproteins, named transferin family. Afinity of Lf to iron is about 260times higher than that of transferin. (1) Lf is present physiologically in exocrine secretions, eg. tears, saliva, milk, sinovial fluid, seminal fluid and in the secondary granules of neutophils. (6) The precise function of Lf in organism is considered to be very complex and is still a hot subject of scientific disputation. Lf was documented to act as antimicrobial, antiinflamatory and antitumoral agent. (15,17) Another of its properties is ability to inhibit hydroxyl radical formation via Fenton reaction. (20) Because of good technological properties and it's physiological occurence Lf can be used as a therapeutical agent.(6) In our experiment we studied the influence of Lf on macroscopical and histological features in liver and kidney of the sewer-rat. We used two-dose model of i.v. Lf ( 50mg/kg in one dose and 3x 20 mg/kg in three days). The tissues of both models were used for histopatological analysis. We observed significant patological changes in kidney and liver after i.v....
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Effect of lactoferrin on macroscopical and histological features in different tissues in rats. I. Cardio-pulmonal system.
Písaříková, Veronika ; Semecký, Vladimír (advisor) ; Mladěnka, Přemysl (referee)
Lactoferin (Lf) is an 80-kDa iron-binding glykoprotein. It shares a high degree of homology at amino acid sequence level and also the three dimensional conformation level with transferrin. Both proteins are classified in the family of iron-binding glykoproteins, named transferrin family. Afinity of Lf to iron is about 260times higher than that of transferrin. (1) Lf is present physiologically in exocrine secretions, eg. tears, saliva, milk, sinovial fluid, seminal fluid and in the secondary granules of neutophils. (6) The precise function of Lf in organism is considered to be very complex and it is still a hot subject of scientific disputation. Lf was documented to act as antimicrobial, antiinflamatory and antitumoral agent. (15,17) Another of its properties is ability to inhibit hydroxyl radical formation via Fenton reaction. (20) Because of good technological properties and its physiological occurence Lf can be used as a therapeutical agent. (6) In our experiment we studied the influence of Lf on macroscopical and histological features in myocard and lung of the sewer-rat. We used two-dose model of i.v. Lf (50mg/kg in one dose and 3x 20 mg/kg in three days). The tissues of both models were used for histopatological analysis. We didn't observe any patological changes in lung. The vessels in myocard...
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The pharmacological therapy of arterial hypertension in special ambulances and general practitioners
Mlčochová, Michaela ; Mladěnka, Přemysl (referee) ; Tilšer, Ivan (advisor)
~ 3 ~ ABSTRACT Topic: Pharmacological treatment of arterial hypertension in specialist ambulance and at general practitioners Made by: Mgr. Michaela Mlčochová OBJECTIVE: The aim of the study is to evaluate and to compare pharmacological treatment of hypertension, effect of pharmacological interventions and risk profile of hypertensive patients in the cardiology ambulance of 1st Department of Medicine, University Hospital in Hradec Králové and in surgeries of general practitioners. METHOD: Only diagnosed, drug-treated hypertensive patients were incuded, fifty patients in each group. We compared medication, achieved blood pressure and risk profile. RESULTS: 78% of patients in the cardiology ambulance and 54% of patients at general practitioners achieved recommended blood pressure levels (BP < 140/90 mmHg). Combined therapy was used in the same rate in the both groups (78%). The most often prescribed medication were beta-blockers in cardiology ambulance and ACE inhibitors and diuretics at general practitioners. Complications of hypertension were more often in the cardiology ambulance (90% vs. 46%), respectively the risk factors were more often in the patients treated by general practitioners (86% vs. 62%). CONCLUSION: The therapy of arterial hypertension was more successful in the cardiology ambulance. But...
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