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The impaired change in plasma long-chain acylcarnitine level as a marker of insulin resistence
Šišmová, Petra ; Nováková, Veronika (advisor) ; Čečková, Martina (referee)
Charles University Faculty of Pharmacy in Hradec Kralove Department of Biophysics and Physical Chemistry Rīga Stradiņš University Latvian Institute of Organic Synthesis Laboratory of Pharmaceutical Pharmacology Candidate: Petra Šišmová Supervisor: Dr. Pharm. Elina Makarova, assoc. prof. Veronika Nováková, Ph.D. Title of the diploma thesis: The impaired change in plasma long-chain acylcarnitine level as a marker of insulin resistance Insulin resistance presents one of the factors that could lead to type 2 diabetes mellitus (T2DM). Increased levels of long-chain (LC)-acylcarnitines are associated with obesity and T2DM and recent studies suggest that LC-acylcarnitines could play a role in the development of insulin resistance. Early diagnosis of insulin resistance would help to prevent the onset of T2DM and the development of associated complications. The purpose of this study was to determine whether the measurements of the changes in acylcarnitine concentrations during the glucose tolerance test (GTT) could be used as a novel marker of insulin resistance. After intraperitoneal administration of glucose in high fat diet (HFD)-fed C57bl/6N, db/db mice and respective controls the concentrations of glucose, insulin, glycated haemoglobin, free fatty acids (FFAs) and acylcarnitine levels in the fasted...
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Current approaches in the treatment of diabetes in pregnancy
Kücük, Pinar ; Čečková, Martina (advisor) ; Vopršalová, Marie (referee)
PINAR KUCUK: Current approaches in the treatment of diabetes in pregnancy. (Diploma thesis) ABSTRACT The management of pregestational diabetes requires tight metabolic control to reduce maternal and perinatal morbidity and mortality. It has been suggested that type I diabetes is a disorder characterized by insulin deficiency and type II diabetes is characterized by insulin resistance. If patient is having type II diabetes, they require higher doses of insulin in pregnancy and limited use of oral hypoglycemic agents; moreover, both type I and type II diabetes mellitus appear to have a necessity of administering different doses of insulin in each trimester. Gestational diabetes mellitus (GDM) is characterized by glucose intolerance of variable severity that begins or is first diagnosed during pregnancy and which shares the same pathophysiology and clinical signs as diabetes mellitus type 2. As well as for a diabetic pregnancy, the therapeutic management of gestational diabetes mellitus must be instituted early and must be intensive. Risk factors for the development of GDM include obesity, older age, family history, previous history of GDM or poor obstetric outcomes, ethnicity, polycystic ovary syndrome and as more recently noted, hypertension. GDM may also be caused by genetic variation that predisposes women...
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Mechanizmy vzniku rezistence vůči platinovým cytostatikům
Bouška, Petr ; Čečková, Martina (advisor) ; Štaud, František (referee)
1. Abstract Although the first platinum drug cisplatin was initially described in 1845, its biological activity was discovered more than 100 years later. Since then are cisplatin and its clinically used analogues carboplatin and oxaliplatin in widespread use for the treatment of variety of human cancers, including ovarian, cervical, head and neck tumors, non-small cell lung, breast, colon, gastric and renal cell carcinoma, sarcoma and relapsed lymphoma. However, the treatment is often accompanied by severe side effects of which nephrotoxicity, peripheral neurotoxicity and myelosuppression are the most serious. Another important obstacle in their clinical use is drug resistance. This thesis evaluates possible mechanisms of the development of platinum drugs resistance. There is a variety of them and they include (i) diminished accumulation of platinum drugs affected by influx transporters (Aquaporin 9, CTR1, OCT1, OCT2) and by efflux transporters (ATP7A, ATP7B,ABCG2); (ii) increased detoxification of drug by thiols glutathione and metallothionein; (iii) improved repair of nuclear lesions affected by NER, MMR, Homologous recombination, and enhanced tolerance to nuclear lesions caused by Replicative bypass, inhibition of pro-apoptic factors (including caspase-3, -8, Fas and other), or by overexpression of...
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Nejnovější přístupy k léčbě Diabetes Mellitus
Hadjiyiangou, Katerina ; Štaud, František (advisor) ; Čečková, Martina (referee)
English abstract Diabetes mellitus (DM) is the best known endocrine disease of the pancreas where the incidence of the affected individuals is increasing rapidly worldwide. It is caused by defects in both the pancreatic islets and in the pancreas to produce enough insulin resulting in impaired glucose homeostasis leading to higher than normal glucose levels in the blood (hyperglycaemia) which is considered to be the hallmark of diabetes. Consequently the main aim of diabetes management is to monitor the glycaemic status. Diabetes mellitus can be subdivided into two classes, type 1 diabetes mellitus (T1DM) which is also known as insulin- dependent diabetes mellitus and type 2 diabetes mellitus (T2DM) which is known as non- insulin-dependent diabetes mellitus. Management of either type of DM requires a number of lifestyle modifications such as increased exercise and decreased weight with the intention of improving metabolic control and enhancing the quality of life. Unfortunately, the majority of patients will eventually require administration of antidiabetic drugs. The present study was performed with the intention of reviewing the currently available scientific literature about both types of DM and discuss the current and novel approaches of treatment, thus giving more emphasis on the novel advances. For...
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Prediction of tacrine-BQCA derivatives across blood-brain-barrier
Vykoukalová, Nikol ; Štaud, František (advisor) ; Čečková, Martina (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Nikol Vykoukalová Supervisor: prof. PharmDr. František Štaud, Ph.D. Title of diploma thesis: Prediction of tacrine-BQCA derivatives across blood-brain-barrier This master thesis deals with the determination of permeability prediction for tacrine BQCA derivatives, potential drugs for Alzheimer's disease, through the blood-brain barrier (BBB) using the method of parallel artificial membrane penetration (PAMPA). We attempted to predict the central bioavailability by the permeability coefficient, to study the relationship between the solubility of the compounds and their log P (or Log D) and the subsequent significance of these data for the prediction of their passage through the blood-brain-barrier. A solution of 1% Pluronic F-127 in PBS was used to solubilize compounds and to ensure the constant concentration during the measurement. The assay was performed so that the solutions of compounds were applied to the donor part of microtiter plate (so-called sandwich arrangement), the bottom compartment was covered by a solution of a polar brain lipid isolated from pig brain (PBL), which serves as a membrane simulating the phospholipid membrane of the brain capillary endothelium. The solution of the...
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Analgesic effects on the fetus development
Velecká, Michaela ; Nachtigal, Petr (advisor) ; Čečková, Martina (referee)
Michaela Velecká Analgesic effects on the fetus development Diploma thesis Charles University in Prague, Faculty of Pharmacy in Hradec Králové Background: The thesis deals with the problems of drug use in cases of inflammatory diseases, hyperthermia and pains of different kind during the pregnancy and the effects of analgesics on fetal development. The aim of this study was to develop a set of expertise and current knowledge in this area and provide the reader with a comprehensive overview of the using of analgesics-antipyretics, non-steroidal analgesics and opioid analgesics, indications for which they are designed, and the causal connection with the disturbances arising in embryo-fetal period of life. Main findings: During pregnancy use pain medication about 50 % of pregnant women in Europe and the USA. Most analgesics may have negative effects on fetal development. Methodology of thesis is based on the study and analysis of the current literature and foreign sources that monitor the reporting of suspected adverse effects of analgesics used during pregnancy and evaluate the results of studies that investigate these reports. In most cases, the results of these studies are controversial and conclusions inconclusive, on the basis of these studies cannot determine with certainty the level of risk of...
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Drug Use Among the University Students - Experiences and Knowledge in Right Using
Suchanková, Veronika ; Klusoňová, Hana (advisor) ; Čečková, Martina (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Candidate: Mgr. Veronika Suchanková Consultant: RNDr. Hana Klusoňová, Ph. D. Title of Thesis: Drug use among the university students- experiences and knowledge in right using Background: - to define a situation in the area of antibiotic and psychopharmaceuticals abuse among the pharmacy students in four different countries (Czech Republic, Great Britain, Australia, Kuwait); - to analyse eventual differences in students' opinions, experiences and attitudes towards these problems, depending on their sex, nationality, and family background; Methods: - anonymous questionaire study; - closed and semi - closed questions; - 800 students (655 females and 145 males) between the age of 16-37 years (average age 19 years); - data analysed in Microsoft Excel 2002 and 2007; - results were obtained through chi - square test; Results: ANTIBIOTICS - the reason of antibiotic use is bacterial infection (36 %), viral infection (25,4 % - from that 8,1 % British and 7,6 % Australians), flu or cold (9,2 %), fever (2,6 % - from that 2,3 % Australians); - ceasing antibiotic usage as instructed by the doctor (95,2 %), after the symptoms of ilness disappear (4,4 %), after the dicrease of fever (0,5 % - from that...
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Therapy of hematologic cancer
Baniková, Lucia ; Štaud, František (advisor) ; Čečková, Martina (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Lucia Baniková Supervisor: Doc. PharmDr. František Štaud, PhD. Title of diploma thesis: Therapy of hematological malignancies Hematologic malignancies are cancers of the blood, bone marrow or lymph nodes. Individual hematological malignancies are defined and distinguished from one another essentially according to four parameters: clinical features, microscopic morphology, immunophenotype and molecular/genetic features. Despite the progress made in the last decade in the treatment of haematological malignancies, most of the patients still have a dismal prognosis. However, the improved knowledge of tumour biology opened the possibility to develop new 'intelligent' therapeutic strategies, the so-named targeted therapies. These approaches aim to selectively kill cancer cells by basing this selectivity on both the expression of a specific molecule on their surface or the activation of particular molecular pathways secondary to malignant transformation. Extensive research has led to the understanding that there are many more subtypes of haematological malignancies. Each of these subtypes behaves in its own particular way and requires its own particular therapy. Correct treatment depends...
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Inhibitors of human enzyme akr1C3 of plant origin
Lojdová, Kateřina ; Novotná, Eva (advisor) ; Čečková, Martina (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Kateřina Lojdová Supervisor: RNDr. Eva Novotná, Ph.D. Consultant: RNDr. Lucie Zemanová, Ph.D. Title of thesis: Inhibitors of human enzyme AKR1C3 of plant origin Enzyme AKR1C3 is a part of large superfamily of aldo-keto reductases. It is a hydroxysteriod dehydrogenase, in human body it participates among others in steroid hormone metabolism but also in activation and deactivation of some drugs. Increased expression of this enzyme is linked to higher aggressivity of some neoplastic diseases and poor prognosis of the treatment, e.g. prostate cancer. This makes AKR1C3 an interesting target for farmaceutical and medical research. Discovery of strong and selective AKR1C3 inhibitor is the first step in finding a drug, that could affect tumor metabolism and restore its sensitivity to treatment. There were 32 naturally occuring compounds from flavonoid and alkaloid groups tested in this study. Its goal was to determine inhibiton efficacy of selected compounds to enzyme AKR1C3. Reduction of a potential anticancer drug oracin to dihydrooracin was used for the measurement, the results were evaluated using an HPLC analysis. IC50 was determined for compounds with significant inhibitory effect.
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