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Metabolic and Genetic Factors of Vascular Ageing
Gelžinský, Július ; Mayer, Otto (advisor) ; Petrák, Ondřej (referee) ; Wohlfahrt, Peter (referee)
Arterial system is a system of vessels distributing blood. Ageing of arterial system leads to two distinct pathologies: atherosclerosis and arteriosclerosis - stiffening of arterial wall. These pathologies can coexist and interfere; however, they differ in their pathogenesis, location, scope and consequences. Progressive loss of elastic properties of large arteries is natural part of vascular ageing. It is directly responsible for several age dependent consequences, such as increase of central systolic pressure or prevalence of isolated systolic hypertension in the elderly. Clinically, central arteries stiffness manifests as aortic pulse wave velocity, which can be quantified, among other methods, using applanation tonometry. There is abundant evidence that aortic pulse wave velocity represents an independent predictor of cardiovascular mortality and morbidity. The most important mechanism in arterial stiffening is repeated mechanical damage which leads to fractures, fragmentation and thinning of elastin. Stiffening of large arteries can be accelerated by several other mechanisms, e.g. deposition of several substances (calcium, advanced glycation end-products, etc.), metabolic turnover of key elements of vascular extracellular matrix (collagen and elastin) or individual genetic susceptibility. In...
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Difficult temperament in early childhood
BAJGAROVÁ, Zdeňka
The presented dissertation consists of both a quantitative part and a qualitative part. The quantitative part deals with the relationship between 5-HTTLPR S/L, MAOA H/L, and COMT Val158Met polymorphisms, the stress reaction of new-born infants after a heel stick blood draw (measured by determining salivary cortisol at three time points) and temperament assessed at age three months by Rothbarth's Infant Behavior Questionnaire-Revised in a sample of 84 infants. Observed polymorphisms were related both to the course of the stress reaction and to temperament. The short allele of serotonin transporter polymorphism was connected to higher scores in the secondary scale of Negative Affect and lower scores in the secondary scale of Attention/Regulation. Homozygotes for the more active allele of MAOA polymorphism (HH) had the lowest scores in Negative Affect compared to both of the remaining groups, they also had higher scores in the secondary scale of Extraversion and Attention/Regulation and a greater decrease of cortisol in comparison to HL heterozygotes. The presence of low-active L allele predisposed their carriers to higher scores in Negative Affect and lower scores in Attention/Regulation. LL homozygotes had the highest increase of cortisol after a heel stick blood draw. The Met allele of COMT Val158Met polymorphism was connected to higher Extraversion and Attention/Regulation and a greater cortisol decrease. It was possible to predict all three secondary scales of IBQ-R from the stress reaction after the heel stick blood draw. Negative Affect was predicted by a higher increase and a lower decrease of cortisol. Extraversion and Attention/Regulation were predicted by a greater cortisol decrease. The magnitude of cortisol decrease partially mediated the influence of COMT Val158Met polymorphism on Extraversion. The qualitative part of the dissertation is a multi-casuistic study of six couples parenting infants with difficult temperaments. It is based on semi-structured interviews that were analysed in accordance with qualitative procedures. The most difficult infant displays to manage were unsoothable crying in the first six months and early sleeplessness and a later escalation of sleeping problems. Mothers were esentially not able to gain control over the amount of crying, but some of them managed to influence their experience to achieve a greater acceptance of it. To do this, it was necessary for them to eliminate their feelings of failure in the parental role. The parents' biggest dilemma concerning their infants' sleeping problems was whether to use the "cry it out" strategy or not to manage them. For some parents parenting a difficult infant was an opportunity to re-evaluate their approach to parenting and the parental role, significantly broadening the concept of both. Caring for a difficult infant significantly strained the marital relationship; four couples experienced marital crisis during the care of their child. The father's involvement in infant care seemed very important in this respect. Insufficient involvement led to dissatisfaction in the mother, the way the mother communicated her demands further influenced the marital relationship. Particular behaviour that the mother understood as the father's involvement in infant care emerged.
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The Heme Catabolic Pathway in Chronic Hepatitis C
Subhanová, Iva ; Zima, Tomáš (advisor) ; Průša, Richard (referee) ; Kráslová, Ivana (referee)
This thesis focuses on the importance of the heme catabolic pathway in chronic hepatitis C (HCV). The aim is mainly to investigate, whether expresion/activity of key enzymes of the heme catabolic pathway, heme oxygenase (HMOX) and biliverdin reductase (BLVRA) in the liver and blood (study A) or promoter variations of HMOX1 and UDP- glucuronosyltransferase (UGT1A1) (study B) may be associated with the progression of fibrosis and may also predict antiviral treatment outcome in patients chronically infected with HCV. We set up a new sensitive method to quantify HMOX activity by reduction gas chromatography. We developed and extensively validated RealTime PCR assay for HMOX and BLVRA expression in the liver and peripheral blood leucocytes (PBL). The (GT)n and (TA)n dinucleotide variations in HMOX1 and UGT1A1 gene promoters, respectively, were determined by fragment analysis. No association was detected between either expression of HMOX/BLVRA or the HMOX1/ UGT1A1 promoter variants and the individual histological stages of liver disease in the HCV positive patients. A marked difference in BLVRA expression in PBL between the sustained responders (SVR) and patients with treatment failure (NVR) was detected before antiviral treatment and during the follow-up. Our data suggests, that BLVRA basal expression...
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