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Phytoextraction of metformin and guanylurea
Kovářová, Kristýna ; Smrček, Stanislav (advisor) ; Petrová, Šárka (referee)
Pharmaceutically Active Compounds include metformin, the most often prescripted drug for a treatment of the diabetes mellitus type 2. Metformin is used in high daily doses (up to 3000 mg per day) and it is eliminated by kidneys in its original non - metabolized form. Metformin is degraded in the wastewater treatment plants to guanylurea. The wastewater treatment plants aren't able to clean the waste water, so metformin and guanylurea enter the environment, especially surface water. This diploma thesis deals with the ability to remove metformin and its environmental metabolite guanylurea via phytoextraction technologies. First experiment was focused on phytoextraction of metformin using 5 plant species - Zea mays L., Pisum sativum L., Avena sativa L., Alternanthera reineckii Mini L. and Staurogyne repens L. Second experiment studied phytoextraction of guanylurea using Zea mays L. and Pisum sativum L. The third experiment deals with the phytoextraction of metformin and guanylurea together using Zea mays L. The media of all plants were contaminated by metformin or guanylurea at different concentration levels. The samples of media were taken in 24 hours intervals during the plant cultivation and the decrease of its concentration were studied by HPLC with UV detection at 233 nm for metformin and 210 nm...
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Effect of biguanides on liver cells metabolism
Švecová, Eliška ; Kalous, Martin (advisor) ; Flachs, Pavel (referee) ; Hansíková, Hana (referee)
The extract from the plant Galega officinalis containing the guanidine derivative galegin has been used in the treatment of diabetes-associated complications since middle ages. Nevertheless, the positive effects of the treatment were often overweight by the adverse side effects. Some sixty years ago guanidin was replaced by the less toxic synthetic biguanide derivatives - metformin, phenphormin and buformin, the latter two being withdrawn due to the unacceptable risk of fatal lactate acidosis. Metformin is still widely used antidiabetics and belongs to the first choice drugs in the treatment of type 2 diabetes. Phenphormin is now gaining renewed attention with regard to its antineoplastic properties. Despite its long-term clinical use the mechanism of biguanides action is not fully understood yet. At present it is generally accepted that the core of its antihyperglycemic effect lays in the inhibition of hepatic gluconeogenesis. In contrast, there is less consensus regarding the particular metabolic pathway or target that are responsible for the metformin-induced attenuation of gluconeogenesis. For a long time, a hot candidate for metformin target in the cell was AMP-activated kinase (AMPK) but the metformin effect was proved also in mice carrying the dominant negative mutation of AMPK α subunit. Quite...
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Effect of biguanides on liver cells metabolism
Švecová, Eliška
The extract from the plant Galega officinalis containing the guanidine derivative galegin has been used in the treatment of diabetes-associated complications since middle ages. Nevertheless, the positive effects of the treatment were often overweight by the adverse side effects. Some sixty years ago guanidin was replaced by the less toxic synthetic biguanide derivatives - metformin, phenformin and buformin, the latter two being withdrawn due to the unacceptable risk of fatal lactate acidosis. Metformin is still widely used antidiabetics and belongs to the first choice drugs in the treatment of type 2 diabetes. Phenformin is now gaining renewed attention with regard to its antineoplastic properties. Despite its long-term clinical use the mechanism of biguanides action is not fully understood yet. At present it is generally accepted that the core of its antihyperglycemic effect lays in the inhibition of hepatic gluconeogenesis. In contrast, there is less consensus regarding the particular metabolic pathway or target that are responsible for the metformin-induced attenuation of gluconeogenesis. For a long time, a hot candidate for metformin target in the cell was AMPK (AMP-activated kinase) but the metformin effect was proved also in mice carrying the dominant negative mutation of AMPK α subunit....
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Phytoextraction of metformin
Kovářová, Kristýna ; Smrček, Stanislav (advisor) ; Zedník, Jiří (referee)
A group of substances including human and veterinary products, cosmetic products, parfumes, drugs, detergents and fertilizers is called the Pharmaceutical and Personal Care Products. PPCPs include also metformin, which is a widely prescripted drug for the treatment of the diabetes mellitus type 2. Metformin isn't metabolized in human body and is eliminated by kidneys in its original form. This way the metformin contamines municipal wastewater. Wastewater treatment plants aren't usually able to clear pollution by pharmaceuticals completely, so part of them gets into the surface water. The ability to eliminate low concentrations of metformin via phytoextraction by Zea mays was studied in this thesis. The media of plants were contaminated by two levels of metformin concentration and during the plant cultivation the samples of media were taken in 24 hours interval. The decrease of metformin concentration in the samples was studied by HPLC with UV detection at 233 nm. The decrease was about 15 - 20 % per one day. Afterwards the extractable residues were analysed by TLC and it was found out, that metformin was extracted only by a root part of the plants. The ability of plants to extract metformin was determined at 0,01 g of metformin per 1 gram of plant per 24 hours.
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The analysis of pharmacotherapy by patients suffering with DM in Greece I
Kalaitzidis, Georgios ; Vlček, Jiří (advisor) ; Doseděl, Martin (referee)
The analysis of pharmacotherapy by patients suffering with DM in Greece I Author: Georgios Kalaitzidis Tutor: Professor RNDr.Jiri Vlcek,CSc. Department of Social and Clinical Pharmacy, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove. Introduction: The diabetes in developed countries concerns 11% of people over 70 years and is the cause of 3% of total deaths in general population. Aim: The aim of the study was to assess the Pharmacotherapy of Diabetes mellitus type II in a pharmacy of a small town of Greece, Veria. Methods: It is retrospective cross-sectional study, which was conducted in a pharmacy in a small town of Greece, Veria. The study population consists of 60 patients with known Type II diabetes Melitus. The data collection was performed by a self-reported questionnaire, which was created and developed by the researcher and filled by the respondents. Results: The mean age of the sample was 56.5±17.5 years. Most of them were females (n=40). Most of the patients knew their fasting glucose level (93.3%,n=56).Of the patients who knew their fasting glucose level, 36 (64.3%) patients had high fasting glucose level and 20 (35.7%) had physiological fasting glucose level. From all the patients(n=60), some of them visited their physician every 6 months (n=24), and every 3 months...
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Effect of metformin on glucose tolerance in relation to fat content in diet
Kuchaříková, Petra ; Horáková, Olga (advisor) ; Škop, Vojtěch (referee)
Prevalence of obesity and associated diseases like type 2 diabetes has increased rapidly during last years. These diseases closely relate to each other. Obesity leads to insulin resistence, which directly precedes type 2 diabetes. Metformin is the most prescribed medicament for type 2 diabetic patients and insulin resistant people. It improves glucose tolerance and insulin resistance. Enzyme AMP-activated protein kinase (AMPK) is strogly involved in metformin action. The latest studies using transgenic models lacking AMPK suggest, that notable part of mechanisms involved in metformin action is independent on AMPK. n-3 polyunsaturated fatty acids (n-3 PUFA), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are abundant in sea fish, have beneficial effects on metabolism. These fatty acids lower plasma lipids and exert cardioprotective effects. n-3 PUFA also prevent development of insulin resistence and type 2 diabetes in rodents. The aim of this thesis was to characterise acute effects of metformin on glucose homeostasis, impact of short term diet intervention with diet rich in n-3 PUFA on metformin action and the role of insulin stimulated signalling pathways and AMPK. Results suggest that early effect of metformin is dose dependent and that single dose of metformin...
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Metabolic effects of chronic metformin administration in obese mice depending on the composition of high-fat diet
Roubalová, Jana ; Rossmeisl, Martin (advisor) ; Vybíral, Stanislav (referee)
Obesity leads to many severe metabolic disorders, e.g. dyslipidemia, insulin resistance, ectopic fat accumulation in the liver and skeletal muscles, non-alcoholic fatty liver disease and finally diabetes mellitus type 2. Metformin (1,1-dimethylbiguanide) is the most favored medicament for the treatment and prevention of these disorders. It stimulates cellular glucose uptake and normalizes blood levels of lipid metabolites without triggering insulin secretion. Research on insulin resistance and diabetes is often realized through developing diet- induced obesity in laboratory animals. The aim of this project is to compare metabolic effects of two different high-fat diets named HFD and HSD. The HFD diet consists chiefly of n-6 polyunsaturated fatty acids (corn oil) and starch (100% glucose). The HSD diet contains mainly saturated fatty acids (lard) and sucrose (50% glucose and 50% fructose). I also studied metabolic effects of metformin by adding it continuously to the drinking water given to obese mice fed with the HFD or the HSD diet. Methods: Intraperitoneal glucose tolerance test (IPGTT), blood and tissue levels of lipid metabolites assessment, radio-immunological assessment of blood levels of insulin, assessment of AMPK activity in liver by western blotting. Results: Increased consumption of the...
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Mass Spectrometry Imaging of Metformin in Tissue Sections
Strnad, Štěpán ; Sýkora, D. ; Vrkoslav, Vladimír ; Cvačka, Josef ; Maletínská, Lenka ; Pirník, Zdenko
Mass spectrometry imaging is a powerful technique suitable for visualization of the distribution of a wide variety of compounds within tissue sections. The main aim of the study was the development and optimization of a sample preparation procedure allowing determination of the distribution of orally dosed metformin in mice kidney sections. Metformin is the first-line medication for the treatment of type 2 diabetes. The optimization of the sample preparation step before imaging experiments included the selection of a suitable matrix and the optimization of various parameters of MALDI analysis. 2,5-dihydroxybenzoic acid was identified as the best matrix providing highest sensitivity. A sublimation method was successfully used for the matrix deposition. The highest relative concentration of metformin was found in the inner zone of kidney 30 minutes after the drug administration.
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