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Metronidazole resistence in clinical cases of giardiasis.
Perglerová, Aneta ; Tůmová, Pavla (advisor) ; Uzlíková, Magdalena (referee)
Metronidazole (MTZ) targets a spectrum of anaerobic pathogens ranging from bacteria to eukaryotic parasites, including the protist Giardia intestinalis (Metamonada). Despite the long time and widespread use of MTZ, understanding giardiasis treatment failure (G-TF) is incomplete. Most of the knowledge was gained on laboratory-generated resistant lines or on clinical lines without data on the treatment outcome. In cooperation with Bulovka University Hospital in Prague, 70 giardiasis cases were followed between 2020-2023, of which 25.7% exhibited the G-TF. Giardia genotyping revealed that G-TF cases belonged to the same genetic group (assemblage B, mainly BIII); and G-TF cases were all imported, out of which 60% were from returning travellers from India. To test the hypothesis that resistance is genetically determined/associated with a transmissible genotype, genetic polymorphisms shared in Giardia G-TF samples in a set of genes involved in MTZ metabolism and detoxifications (NR1, NR2, prx1, hmp) were examined. The analysis revealed amino acid substitutions (K42E, K139R) in NR2 isolates of G-TF patients, which might affect protein structure. Also, a gene dosage effect as drug resistance co-variant/cause due to gene duplications or deletions of the hmp gene was tested. Results from dPCR revealed that...
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The role of C-reactive protein in cardiac ischemic tolerance
Perglerová, Aneta ; Neckář, Jan (advisor) ; Vebr, Pavel (referee)
Ischemic heart disease (CHD) is a set of pathophysiological states, disorders of blood flow and oxygen supply of the myocardium due to vascular constriction or thrombus blockage. Inflammation plays an important role in CHD. The inflammatory response is associated with the synthesis of acute phase proteins in the liver such as C-reactive protein (CRP). CRP plays an important role in acute forms of CHD such as myocardial infarction (MI). The development of CHD may be supported by the occurrence of some of the risk factors (eg. atherosclerosis, hypertension, plasma CRP). Increased CRP levels may support the initiation of atherosclerotic plaque formation as well as in the case of hypertension the presence of CRP increases the risk of developing CHD. The healing proces after acute MI is accompanied by an inflammatory phase where CRP occurs naturally and CRP is important to accelerate inflammation. There may be a situation which inflammation goes into a chronic phase because it is not terminated in time, with constant CRP synthesis. High levels of CRP may decrease the prognosis after MI. The elevated plasma CRP has a negative effect on the expansion of MI and the associated ventricular dilatation, which may result in a rupture of the cardiac wall. Hypertrophy is the compensatory mechanism of the...
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The role of C-reactive protein in cardiac ischemic tolerance
Perglerová, Aneta ; Neckář, Jan (advisor) ; Vebr, Pavel (referee)
Ischemic heart disease (CHD) is a set of pathophysiological states, disorders of blood flow and oxygen supply of the myocardium due to vascular constriction or thrombus blockage. Inflammation plays an important role in CHD. The inflammatory response is associated with the synthesis of acute phase proteins in the liver such as C-reactive protein (CRP). CRP plays an important role in acute forms of CHD such as myocardial infarction (MI). The development of CHD may be supported by the occurrence of some of the risk factors (eg. atherosclerosis, hypertension, plasma CRP). Increased CRP levels may support the initiation of atherosclerotic plaque formation as well as in the case of hypertension the presence of CRP increases the risk of developing CHD. The healing proces after acute MI is accompanied by an inflammatory phase where CRP occurs naturally and CRP is important to accelerate inflammation. There may be a situation which inflammation goes into a chronic phase because it is not terminated in time, with constant CRP synthesis. High levels of CRP may decrease the prognosis after MI. The elevated plasma CRP has a negative effect on the expansion of MI and the associated ventricular dilatation, which may result in a rupture of the cardiac wall. Hypertrophy is the compensatory mechanism of the...
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