National Repository of Grey Literature 97 records found  1 - 10nextend  jump to record: Search took 0.01 seconds. 
Characterization of different differentiation protocols of H9c2 cardiomyoblasts
Gardianová, Anna ; Jirkovský, Eduard (advisor) ; Macháček, Miloslav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Anna Gardianová Supervisor: PharmDr. Eduard Jirkovský, Ph.D. Title of diploma thesis: Characterization of different differentiation protocols of H9c2 cardiomyoblasts Cell differentiation is a common process in the development of multicellular organisms leading to an alteration of cell's appearance and function. The process of differentiation plays a significant role in the reparation of damaged tissues too. Some chemicals may have negative effects on these processes and therefore affect human health. This thesis focuses on characterization of differentiation processes of H9c2 cell line using various published differentiation protocols, and to describe changes over time in the morphology (occurrence of multinucleated and elongated cells) and mRNA expression of selected markers typical for the cardiac (cTnT, Hand2, GATA4) or skeletal (myogenin) muscle phenotype. We monitored the process of the differentiation for 15 days and the individual protocols differed by the addition of fetal bovine serum (FBS, 1 % or 10 %) and all-trans- retinoic acid (ATRA, 10 nmol/L) to the growth medium Dulbecco's Modified Eagle's Medium. From what we have observed, the results show that all of the utilized protocols...
Monitoring the antioxidant activity of newly synthesized potential acetylcholinesterase modulators
Keratová, Žaneta ; Macháček, Miloslav (advisor) ; Kobrlová, Tereza (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Žaneta Keratová Supervisor: RNDr. Miloslav Macháček, Ph.D. Consultant: RNDr. Ľubica Múčková, Ph.D. Title of diploma thesis: Monitoring the antioxidant activity of newly synthesized potential acetylcholinesterase modulators. The theoretical part of the diploma thesis focuses on the characteristics of oxidative stress (OS) and antioxidant protection of the organism. In the next part, neurodegenerative diseases and the importance of OS in their development are discussed in detail. In the experimental part, the cytotoxicity of new potential acetylcholinesterase modulators was evaluated using the neuroblastoma cell line SH-SY5Y. The cytotoxicity of the compounds, expressed as IC50, was measured by a colorimetric method using the tetrazolium salt (MTT). This method was also used to determine the maximum tolerated concentration (MTC). These values were subsequently validated by measuring the apoptotic profile of cells in a physiological environment (without OS) and hydrogen peroxide (H2O2)-induced OS using microcapillary flow cytometry. The results showed that the compounds did not induce any statistically significant change in the distribution of cells in each population. Subsequently, the antioxidant...
Study of migration of cells affected by sulfur mustard
Mojská, Mária ; Macháček, Miloslav (advisor) ; Fikrová, Petra (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mária Mojská Supervisor: RNDr. Miloslav Macháček, PhD. Consultant: Mgr. Petr Jošt, PhD. Title of diploma thesis: Study of the migration of cells affected by sulfur mustard Sulfur mustard is a highly toxic chemical agent. From the point of view of toxicology, it is classified as a blistering agent, and its use is prohibited by the Chemical Weapons Convention. However, this substance has been used in several armed conflicts and terrorist attacks in the past. When it comes in contact with human skin, it produces typical blisters filled with a yellowish exudate. Sulfur mustard has cytotoxic and cytostatic effects on living tissue, and therefore the treatment of such lesions is extremely difficult. This thesis is focused on the in vitro evaluation of the possibility of employing growth factors IGF, KGF, and EGF in the wounding process of sulfur mustard-damaged tissue. The effect of these growth factors on collective migration of HaCaT keratinocytes and HDFa skin fibroblasts under in vitro conditions was evaluated using the "scratch wound healing assay" method. Our results show that the toxic effects of sulfur mustard inhibit cell migration to such an extent that the positive effect of the growth...
Peripherally substituted subphthalocyanines for photodynamic therapy with benzocrown or tyrosine methyl ester as axial ligands
Hlbočanová, Ingrid ; Macháček, Miloslav (advisor) ; Šimůnek, Tomáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Science Candidate: BSc. Ingrid Hlbočanová Supervisor: RNDr. Miloslav Macháček, Ph.D. Title of diploma thesis: Peripherally substituted subphtalocyanines for photodynamic therapy with benzocrown or tyrosine methyl ester as axial ligands Tumor diseases are slowly but surely becoming the most widespread disease in the world. Malignant conditions affect a wide range of people who inherited a predisposition to the disease genetically, or were influenced by environmental factors. However, expensive therapy is a problem not only in developed countries, but especially in third world countries. Financial aspect and availability are only part of the problem. Early diagnosis, prevention before the onset of this type of disease and effective therapy are the key elements to succesfull treatment. Due to the high prevalence and mortality associated with malignant diseases, which are increasing every year, great efforts are devoted to the prevention of these diseases and the correct and timely diagnosis associated with a healthy lifestyle. Great attention is also paid to the research and development of new and effective anti-tumor drugs and therapeutic approaches. One such modern and promising method is photodynamic therapy (PDT)....
New inhibitors of topoisomerase II - study of antiproliferative effects and influence on antitumor activity of etoposide
Proftová, Lenka ; Šimůnek, Tomáš (advisor) ; Macháček, Miloslav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Lenka Ohnemichlová Supervisor: prof. PharmDr. Tomáš Šimůnek, PhD. Title of diploma thesis: New inhibitors of topoisomerase II - study of antiproliferative effects and influence on antitumor activity of etoposide Cancer is a serious societal health problem, which can affect each of us, and its incidence increases rapidly with age. Anthracycline antibiotics (ANT) are extremely effective drugs that have been used to treat a number of cancers. They have a multimodal mechanism of action, one of them being the inhibition of topoisomerase 2 (TOP2), an essential cellular enzyme modulating DNA topology. Currently, use of ANTs is limited due to concerns about the occurrence of cardiotoxicity. Etoposide (ETO) is an antitumor agent that acts as topoisomerase poison. ETO is often used in combination therapy with ANTs, but it is not considered significantly cardiotoxic. Dexrazoxane (DEX) is the only approved cardioprotectant against cardiotoxicity of ANTs. However, it does not act as chelating agent, as previously thought, but through inhibition of TOP2. Although DEX has been shown to be a very potent cardioprotectant, it also has its disadvantages. DEX has been associated with the occurrence of secondary...
Comparison of the effect of bisphenols on parental and differentiated H9c2 cells
Macáková, Barbora ; Jirkovský, Eduard (advisor) ; Macháček, Miloslav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Barbora Macáková Supervisor: PharmDr. Eduard Jirkovský, Ph.D. Title of diploma thesis: Comparison of the effect of bisphenols on parental and differentiated H9c2 cells Bisphenol is compound largely found in products and environment around us. Its toxicity and danger for human health is still being studied, meanwhile direct influence of environmentally relevant doses was not discovered. These endocrine disruptors are affecting variousreceptorsin bodiesand effecton cardiovascularsystem isnotexcludedeither.The most extensively studied substance is BPA, which is gradually being replaced by its analogs, although these are not extensively researched to the same extent. In this work we focused on influence of bisphenol BP, M and S on differentiation of H9c2 cells, serving as a model with potential negative effects on heart development and its regeneration after damage. H9c2 cell line has an undifferentiated phenotype but can be easily directed towards differentiation under certain conditions Research was focused on impact of bisphenol on differentiated cells and its changes in the expression of selected differentiation markers (GATA4, Hand2, Tnnt2, Myog) (transcription factors). Set protocols were...
Anti-tumor and immunomodulatory effect of polymer conjugates based on HPMA carrying gemcitabine
Klusová, Natálie ; Beránek, Martin (advisor) ; Macháček, Miloslav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Natálie Klusová Supervisor: prof. PharmDr. Martin Beránek, Ph.D. Consultant: RNDr. Milada Šírová, Ph.D. Title of diploma thesis: Anti-tumor and immunomodulatory effect of polymer conjugates based on HPMA carrying gemcitabine The diploma thesis is focused on the anti-tumor and immunomodulatory effect of polymer conjugates based on HPMA carrying gemcitabine (Gem). We investigated the effects of four polymer conjugates (P-Gem1-P-Gem4), which had similar molecular weight and carried approximately the same amount of the drug. The only difference were the used spacers for Gem linkage. We used the following spacers: β-Alanin (P-Gem1); glycyl-phenylalanyl- leucyl-glycyl (P-Gem2); aminocaproic acid (P-Gem3); valeric acid (P-Gem4). Based on the assessed IC50 values for tumor cell lines 4T1, LL2, Panc02, MiaPaca2 and Panc1 the samples were divided into two groups: a) samples with quick rate of Gem release (P- Gem1, P-Gem2); b) samples with slow rate of Gem release (P-Gem3, P-Gem4). The in vivo stability of the conjugate affects systemic toxicity and anti-tumor activity, which was proven by the experiment performed on BALB/c mice bearing murine mammary carcinoma cells (4T1). We enrolled significant...
Evaluation of cytotoxicity of newly synthesized phenoxytacrine derivatives as potential therapeutics of Alzheimer's dementia
Koperová, Erika ; Macháček, Miloslav (advisor) ; Múčková, Ľubica (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Erika Koperová Supervisor: RNDr. Miloslav Macháček, Ph.D. Supervisor-consultant: RNDr. Tereza Kobrlová, Ph.D. Title of diploma thesis: Evaluation of cytotoxicity of newly synthesized phenoxytacrine derivatives as potential therapeutics of Alzheimer's dementia. The increasing prevalence of Alzheimer's disease and the availability of mainly symptomatic treatment as opposed to causal therapy require the development of new drugs that affect the complex pathogenesis of this condition. Recently, the prevailing effort to create compounds with a multimodal effect and lower toxicity compared to Tacrine has led to the synthesis of phenoxytacrine and its derivatives. These substances, due to their targeting of multiple targets simultaneously, appear to be suitable candidates for the treatment of Alzheimer's disease. The subject of this thesis is the determination of the cytotoxicity of phenoxytacrine derivatives and the evaluation of its relationship to the structure of the studied compounds. Cytotoxicity studies are an important aspect of drug development, determining the effect of a specific chemical compound on living cells. This type of study is crucial for understanding the potential toxicity of new...
Acromegaly in patients with somatotroph pituitary adenomas - determining the expression level of proteins with а potential influence on the therapeutic response
Krbalová, Lenka ; Macháček, Miloslav (advisor) ; Pejchal, Jaroslav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: RNDr. Mgr. Lenka Krbalová Supervisor: RNDr. Miloslav Macháček, Ph.D. Consultant Supervisor: MUDr. Jiří Soukup, Ph.D. Title of the rigorous thesis: Acromegaly in patients with somatotroph pituitary adenomas - determining the expression level of proteins with a potential influence on the therapeutic response Acromegaly is a rare disease manifested by a wide variety of symptoms (enlargement of the acral parts of the body, macroglossia, neuropathy, hypertension, cardiomyopathy etc.). These symptoms significantly decrease quality of life and shorten life span. It is caused by increased secretion of growth hormone in adulthood. The cause of this increased secretion is most often a somatotroph adenoma. In most cases, the treatment of acromegaly requires a comprehensive approach. It is a combination of surgical intervention, radiotherapy and pharmacotherapy. Somatostatin analogues are mainly used in pharmacotherapy. These compounds have similar pharmacodynamic effects as somatostatin after binding to the somatostatin receptor. The administration of these compounds leads to a decrease in the secretory activity of the tumour and subsequently to the reduction of its volume. Octreotide and lanreotide belong...

National Repository of Grey Literature : 97 records found   1 - 10nextend  jump to record:
See also: similar author names
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6 Macháček, Marek
19 Macháček, Martin
4 Macháček, Matouš
2 Macháček, Michael
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3 Macháček, Miroslav
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