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Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Bc. Ladislava Cablíková Supervisors: Ass. Prof. Mojca Božič-Mijovski, Ph.D., prof. PharmDr. Petr Pávek, Ph.D., RNDr. Jana Nekvindová, Ph.D. Thesis title: The Impact of Apixaban on Overall Hemostatic Potential Disorders at certain levels of the complicated haemostatic system can lead to either bleeding or excessive blood coagulation. These pathological conditions are treated with anticoagulants, which aim to correct excessive coagulation. However, traditional anticoagulant therapy has many limitations, which initiated efforts to develop oral anticoagulants with a better profile. These new-generation anticoagulants are called DOAC - Direct Oral AntiCoagulans. Apixaban, as one of xabans, has predictable pharmacokinetics and pharmacodynamics and therefore does not require a routine laboratory monitoring of the treatment effect. Nevertheless, it still requires evaluation in urgent clinical situations. Standard coagulation screening assays, e.g., PT (prothrombin test) and APTT (activated partial thromboplastin test), do not fully reflect the actual status of the drug. Therefore, researchers aim is to find a relatively simple and fast hemostatic assay that would correlate with the actual condition...

This work is focused on issue of manufacture of fresh cheeses with using plant coagulants.Cheese is milk product, which is produced by precipitation of milk protein by rennet or other suitable coagulant agents. Plant extracts have been used to coagulate milk in antiquity, although there are very few knowledges of their properties. A lot of interest in vegetable coagulants was in 1960, when the increasing consumption of cheese was not enough of animal rennet. The literary section described the manufacture of cheese, characteristic of different type of coagulant and properties of different plant coagulants, which are used in different parts of the world. The aim of practical part was made fresh cheeses coagulated by plant extracts. The cheeses coagulated at different temperatures. It was measured pH and mass of arising cheese. It was also carried out microbiological analysis of cheeses, plant coagulants and milk. The work concentrated mainly on optimizing the temperature coagulation of milk and cheese properties.

On vessel wall injury the complex process of blood coagulation is set off. It is composed of vasoconstriction, primary hemostasis, secondary hemostasis and fibrinolysis. This work enriches current model of primary hemostasis of Storti. The previous model used ALE formalism for tracing of development of platelet plug. The phase field method is used for tracing of the development of interface blood-thrombus. Storti's primary hemostasis was extended to capture the fact, that the platelets can be activated in the blood flow in the area of reactive surface not only by influence of chemical agents like thromboxane, ADP and thrombin but also by their exposure to elevated values of shear stress. In our first approach we deal the emerging thrombus as a fluid with very high viscosity. In the second approach it was assumed, that platelet plug develops as a viscoelastic material according to constitutive equations of clot introduced by Kempen. In this manner platelet clot matures into blood clot. In both approaches the blood is represented as a non-Newtonian fluid. The framework of the phase field method was applied also to the model of high shear rate thrombosis of Weller. Weller's original model of Weller took advantage of the cylindrical symmetry of computational domains for its computations, hence the...

This Master thesis called Comparison of methods for measuring milk coagulation deals with a major technological step in the production of cheese, which is the process of curdling of milk. Two methods for measuring this process were compared, particularly the visual and instrumental method utilizing nephelo-turbidimeter. Based on statistical data processing in three cases, a difference was observered between the average visual measurement and instrumental measurement of significant 99%. Furthermore, the impacts on curdling of milk were assessed what showed that the best default property for the process of curdling had a pasteurized milk sample with the addition of CaCl2. On the basis of calculations in this thesis it has been concluded that to curdle a 100 l of milk with rennet CHY-MAX a 0,2 liters of the rennet is required. The same amount of milk is curdled with 1 litre of rennet Lactochym. In assessing the economics of using rennet Lactochym and CHY-MAX it has been found that for cost optimization it is more appropriate to use rennet CHY-MAX with a strentgh of at least 190 IMCU/ml diluted in distilled water at a ratio of 1:5.

The aim of this diploma thesis is to explore the coagulation phase in water treatment process from two perspectives, the removal of cyanotoxin microcystin and the responses of ecotoxicological indicator species Daphnia magna to different concentration of this toxin, contained in a sample of cyanobacterial water bloom, which was extracted from a dam and was dominated by cyanobacteria Microcystis aeruginosa. The sample was administered in three environmentally relevant concentrations to 6 clones of Daphnia magna, 3 of which had previous experience with M. aeruginosa. Coagulation process was performed under optimal conditions: pH = 6.36; KNK4,5 = 0.26 mmol.l-1 ; Fe = 0.162 mg.l-1 ; DOC = 2.83 mg.l-1 using 10 ml of 0.125M NaHCO3 in two litres of ultrapure water. Individual forms of microcystin were detected in this ratio: 31.6 % MC-LR, 53.6 % MC-RR and 14.8 % MC-YR. The study has shown that under these conditions coagulation does not remove microcystin, e.g. the efficiency of the process is zero. In ecotoxicological study, with growing concentration of cyanobacterial mixture the negative impact on Daphnia magna increased. We have found interclonal variability in responses of D. magna, however, the previous experience with M. aeruginosa had no effect. With growing concentration of cyanobacterial water...

Factor C is a multi-domain serine protease which recognizes Gram-negative bacteria via binding to lipopolysaccharides and triggers hemolymph clotting cascade in the horseshoe crab. A closely related molecule was also found to be present in the genome of the tick Ixodes scapularis. In this work, the full sequence of Factor C ortholog from Ixodes ricinus (IrFC) was determined. IrFC is mainly expressed in tick hemocytes and the heavy chain of the activated molecules is present in tick hemolymph as confirmed by Western blotting with antibodies raised against recombinant fragments of IrFC. The function of the IrFC in tick innate immunity was assessed using its silencing by RNA interference.

The Use of Thromboelastography in Evaluation of Coagulation in Females with Physiological or Pathological Pregnancy MUDr. Ferdinand Polák Abstract Introduction: The target of this study was to compare thromboelastography coagulation parameters in the following three groups: a) healthy pregnant women, b) healthy non-pregnant women and c) pregnant women with pathological pregnancy and also to compare it to reference limits for the common population. If appropriate, we would propose recommendations for new reference ranges for pregnant women in their third trimester. Materials and methods: Prospective observational study, comparing, by using thromboelastography, the blood samples of 60 healthy women in their third trimester of pregnancy (group GRAV) to the samples of the control group of 43 healthy non-pregnant fertile women (group NON-GRAV) and to the samples of 50 women with pathological pregnancy (preeclampsia, fetal death) in their third trimester (group PATOL). Selective percentiles were used to determine new reference limits. Results and conclusions: We found statistically significant differences between groups GRAV and NON-GRAV. Therefore, we established, based on our results, new thromboelastography reference limits for pregnant women. Coagulation changes during pathological pregnancy are less...

Intrusion of pharmaceuticals into surface and drinking water is nowadays a problem, that is solved all over the world. This diploma thesis is focused on the removal of pharmaceuticals from water by coagulation. The efficiency of two coagulant agents - chitosan and ferric sulphate was compared. For comparison was used adsorption on a granular-activated-carbon. Efficiency of removal was investigated by UV-VIS spectrophotometer and HPLC.

This work is focused on improvement of particle formation and separation processes in drinking water. These include the comparison of the dynamics of different coagulation reagents (aluminum sulphate and ferric sulphate) to find the optimal dose of coagulant. During centrifugation test is important to find such a setting centrifuge where we get the best results. In this work we studied the influence of the total mineralization at the optimum dose of coagulant.