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Ultrasonographic Markers of Infection-Related Complications in Preterm Prelabour Rupture of Membranes
Špaček, Richard ; Kacerovský, Marian (advisor) ; Pařízek, Antonín (referee) ; Hruban, Lukáš (referee)
Preterm prelabour rupture of membranes (PPROM) represents a serious pregnancy complication associated with approximately 30% of preterm deliveries. PPROM might be complicated by the presence of microorganisms and/or their nucleic acids in amniotic fluid termed microbial invasion of the amniotic cavity (MIAC), and the elevation of various inflammatory mediators in the amniotic fluid referred to as intra-amniotic inflammation (IAI). Based on their presence or absence, four subgroups of PPROM can be defined: i) intra-amniotic infection (presence of both MIAC and IAI), ii) sterile IAI (IAI alone), iii) colonisation of the amniotic cavity (MIAC alone), and iv) absence of both MIAC and IAI. Although gestational age at delivery is the most important factor affecting the risk of neonatal morbidity and mortality, the presence of MIAC and/or IAI might worsen neonatal outcomes. Therefore, precise assessment of the intra-amniotic environment seems essential for ideal personalised management of PPROM pregnancies. Modern ultrasound machines allow a very detailed examination of the foetus. The effort to identify surrogate ultrasound markers of MIAC and/or IAI represents a logical research step in this field. One of the most promising results has been found on doppler assessment on blood flow in the foetal splenic...
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Study of interactions of antiviral drugs with selected placental transporters
Karbanová, Sára ; Štaud, František (advisor) ; Kacerovský, Marian (referee) ; Mladěnka, Přemysl (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Sára Karbanová, MSc. Supervisor: prof. PharmDr. František Štaud, Ph.D. Consultant: doc. PharmDr. Lukáš Červený, Ph.D. Title of Dissertation Thesis: Study of interactions of antiviral drugs with selected placental transporters The backbone of HIV treatment in pregnant women is the combination antiretroviral therapy which effectively suppresses the viral proliferation in maternal blood circulation. One of drugs in this therapy regimen should be a molecule with high placental transfer to assure the prophylaxis of viral transfer to fetus. There is no approved guideline for pharmacotherapy of pregnant women infected with hepatitis C (HCV), however recent evidence suggests that lowering the maternal viral load could correlate with lower likelihood of HCV transmission to the fetus. To assure and further develop the effective and safe pharmacotherapeutic approaches for treatment of HIV and HCV in pregnancy with respect to fetal safety, it is essential to understand mechanisms of placental transfer of anti(retro)viral drugs. In this Dissertation thesis we focused on molecules derived from nucleosides (anti-HIV abacavir, emtricitabine, zidovudine, tenofovir disoproxil fumarate and anti-HCV...
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The clinical application of bioimpedance spectroscopy in polytrauma patients and in pregnant women
Josková, Věra ; Hronek, Miloslav (advisor) ; Kacerovský, Marian (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Candidate: Mgr. Věra Josková Supervisor: doc. PharmDr. Miloslav Hronek, Ph.D. Title of Doctoral Thesis: The clinical application of bioimpedance spectroscopy in polytrauma patients and in pregnant women Introduction and Objectives: Bioimpedance spectroscopy (BIS) is a non-invasive method determining the amount of body fluids and their distribution into the extracellular (ECW) and intracellular (ICW) space, based on the tissue resistance. It has already been applied in many clinical trials in healthy volunteers and in different groups of patients to assess body composition. Furthermore, it seems to be useful in nutritional counseling. However, in critically ill patients hospitalized in intensive care unit (ICU) or in pregnant women, this method has not been used in routine clinical practice as yet. Both of these groups are characterized by the state of increased body fluids. For this reason, BIS could be applied in respective groups of patients. Hence, the main aims of this doctoral thesis were: 1) to describe in detail the principle and the previous use of BIS; 2) to use the BIS to determine the degree of hyperhydratation of patients with polytrauma (PP), and to evaluate the results with the...
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Soluble form of the scavenger receptor for hemoglobin (sCD163) in pregnancies complicated by preterm prelabor rupture of membranes
Kacerovský, Marian ; Tošner, Jindřich (advisor) ; Calda, Pavel (referee) ; Procházka, Martin (referee)
Preterm prelabor rupture of membranes (PPROM) is responsible for approximately 30% of all preterm deliveries. Histological chorioamnionitis (HCA) has been found in 50-80% of PPROM cases and is associated with higher rates of adverse maternal and neonatal outcome. The scavenger receptor for hemoglobin (CD163) is a transmembrane glycoprotein expressed almost exclusively on monocytes and macrophages. Its main function is the binding of hemoglobin-haptoglobin complexes. CD163 also serves as a surface receptor that recognizes intact bacteria and triggers cytokine production function. Moreover, it participates in the late down-regulatory phase of both acute and chronic inflammation. The soluble form of CD163 (sCD163) most likely represents the extracellular domain of CD163, which can be shed from the surface and released into the body fluid. The main aim of this thesis was to investigate sCD163 in pregnancy complicated by PPROM and relationships with HCA and funisitis. The first specific aim was to determine amniotic fluid sCD163 levels in uncomplicated pregnancies. Amniotic fluid samples were taken from 31 women who underwent amniocentesis for genetic testing in the second trimester, as well as from 32 women at term, 21 of whom had and 11 of whom did not have uterine contractions. The sCD163 levels in...
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New Aneuploidy Ultrasound Markers in First Trimester of Pregnancy
Břešťák, Miroslav ; Calda, Pavel (advisor) ; Kacerovský, Marian (referee) ; Baxová, Alice (referee)
Prenatal diagnostics is headed in several directions - towards visualization of fetuses and biochemical, cytogenetic and molecular genetic diagnostics in laboratories. Whereas visualization of fetuses does not a priori represent any direct risk for pregnancy and does not increase the number of potential pregnancy complications, this is not always the case with the laboratory testing. There are known risks connected with invasive methods of prenatal diagnostics. The number of potential unintentional pregnancy complications and losses as well as the technical and economic aspects of invasive prenatal diagnostics lead to attempts of identifying ways of detecting any potentially affected individuals by screening methods, thus minimizing the undesirable impact of invasive diagnostics on the pregnant population. The more precise the selective criteria, the lesser the number of pregnant women exposed to invasive exams. Another way of decreasing the number of unintentional complications in relation to invasive diagnostics is to simplify and improve the fetal samples harvesting methods during pregnancy. The work primarily focused on two areas: Determination of the relation between fraction shortening of the left and right ventricles and a fetal chromosomal complement, and verification of reliability of a new method...
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Diagnosis and therapy of intrauterine pathologies associated with pregnancy.
Švabíková, Lucie ; Žižka, Zdeněk (advisor) ; Novotný, Zdeněk (referee) ; Kacerovský, Marian (referee)
Introduction: Actually 0.7-1 percent of all deliveries can be followed by secondary uterine bleeding. There is a residual trophoblastic tissue diagnosed in most of these cases and it is often managed by repeat intrauterine interventions. These operations are connected with high risk of formation of intrauterine adhesions and their early diagnosis and management can be important for next fertility. Material and methods: There were generally 188 patients included into the study. All patients underwent ultrasound examination in 6 weeks after delivery and ambulant hysteroscopy after next 2 months without anesthesia. Described intrauterine pathologies (residual tissue and adhesions) were managed in one step. Results: In cases with suspect ultrasound finding, the retained trophoblastic tissue was diagnosed by hysteroscopy in 66 percent vs. in 96 percent with sensitivity 85 percent and specificity 85 percent. Patients with intrauterine adhesions had normal ultrasound finding in 74 percent and it did not recognized patients with severe adhesions in 94 percent. Clinical signs had generally 72 percent of patients with diagnosed left residual tissue. Number of severe residual tissue is increasing with delay of instrumental evacuation from delivery (10 vs. 30 percent). When is necessary to repeat the operation...
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Interactions of selected antiretroviral drugs and methylmercury with placental membrane transporters
Ťupová, Lenka ; Čečková, Martina (advisor) ; Fusek, Josef (referee) ; Kacerovský, Marian (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Mgr. Lenka Ťupová Supervisor: doc. PharmDr. Martina Čečková, Ph.D. Title of doctoral thesis: Interactions of selected antiretroviral drugs and methylmercury with placental membrane transporters. Pregnant women are especially in developed countries exposed to high amount of various xenobiotic including environmental pollutants and drugs. Antiretroviral therapy (ART) is administered to HIV positive pregnant women for the purpose of prevention of HIV mother- to-child-transmission. Pharmacokinetics of many antiretrovirals is limited or enhanced by activity of ATP-binding cassette (ABC) or Solute carrier's transporters, of which many are expressed also in placental tissue. ART therapy usually consists of combination of 3 - 4 antiretroviral drugs, thereby leading to higher risk for development of drug-drug interactions on ABC and SLC transporters. In this study we described influence of non-nucleoside reverse transcriptase inhibitors etravirin and rilpivirin on BCRP- and MDR1-mediated transport of tenofovir disoproxil fumarate (TDF) and/or abacavir. Etravirin showed potent inhibition of BCRP transporter significantly changing transport of both, TDF and abacavir, across monolayers of MDCKII-BCRP...
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Study of interactions of antiviral drugs with selected placental transporters
Karbanová, Sára ; Štaud, František (advisor) ; Kacerovský, Marian (referee) ; Mladěnka, Přemysl (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Sára Karbanová, MSc. Supervisor: prof. PharmDr. František Štaud, Ph.D. Consultant: doc. PharmDr. Lukáš Červený, Ph.D. Title of Dissertation Thesis: Study of interactions of antiviral drugs with selected placental transporters The backbone of HIV treatment in pregnant women is the combination antiretroviral therapy which effectively suppresses the viral proliferation in maternal blood circulation. One of drugs in this therapy regimen should be a molecule with high placental transfer to assure the prophylaxis of viral transfer to fetus. There is no approved guideline for pharmacotherapy of pregnant women infected with hepatitis C (HCV), however recent evidence suggests that lowering the maternal viral load could correlate with lower likelihood of HCV transmission to the fetus. To assure and further develop the effective and safe pharmacotherapeutic approaches for treatment of HIV and HCV in pregnancy with respect to fetal safety, it is essential to understand mechanisms of placental transfer of anti(retro)viral drugs. In this Dissertation thesis we focused on molecules derived from nucleosides (anti-HIV abacavir, emtricitabine, zidovudine, tenofovir disoproxil fumarate and anti-HCV...
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Interactions of selected antiretroviral drugs and methylmercury with placental membrane transporters
Ťupová, Lenka ; Čečková, Martina (advisor) ; Fusek, Josef (referee) ; Kacerovský, Marian (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Mgr. Lenka Ťupová Supervisor: doc. PharmDr. Martina Čečková, Ph.D. Title of doctoral thesis: Interactions of selected antiretroviral drugs and methylmercury with placental membrane transporters. Pregnant women are especially in developed countries exposed to high amount of various xenobiotic including environmental pollutants and drugs. Antiretroviral therapy (ART) is administered to HIV positive pregnant women for the purpose of prevention of HIV mother- to-child-transmission. Pharmacokinetics of many antiretrovirals is limited or enhanced by activity of ATP-binding cassette (ABC) or Solute carrier's transporters, of which many are expressed also in placental tissue. ART therapy usually consists of combination of 3 - 4 antiretroviral drugs, thereby leading to higher risk for development of drug-drug interactions on ABC and SLC transporters. In this study we described influence of non-nucleoside reverse transcriptase inhibitors etravirin and rilpivirin on BCRP- and MDR1-mediated transport of tenofovir disoproxil fumarate (TDF) and/or abacavir. Etravirin showed potent inhibition of BCRP transporter significantly changing transport of both, TDF and abacavir, across monolayers of MDCKII-BCRP...
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Study of interactions of antiviral drugs with selected placental transporters
Karbanová, Sára ; Štaud, František (advisor) ; Kacerovský, Marian (referee) ; Mladěnka, Přemysl (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Sára Karbanová, MSc. Supervisor: prof. PharmDr. František Štaud, Ph.D. Consultant: doc. PharmDr. Lukáš Červený, Ph.D. Title of Dissertation Thesis: Study of interactions of antiviral drugs with selected placental transporters The backbone of HIV treatment in pregnant women is the combination antiretroviral therapy which effectively suppresses the viral proliferation in maternal blood circulation. One of drugs in this therapy regimen should be a molecule with high placental transfer to assure the prophylaxis of viral transfer to fetus. There is no approved guideline for pharmacotherapy of pregnant women infected with hepatitis C (HCV), however recent evidence suggests that lowering the maternal viral load could correlate with lower likelihood of HCV transmission to the fetus. To assure and further develop the effective and safe pharmacotherapeutic approaches for treatment of HIV and HCV in pregnancy with respect to fetal safety, it is essential to understand mechanisms of placental transfer of anti(retro)viral drugs. In this Dissertation thesis we focused on molecules derived from nucleosides (anti-HIV abacavir, emtricitabine, zidovudine, tenofovir disoproxil fumarate and anti-HCV...
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