The prognostic value of E-cadherin and Ki-67 compared to standard histopathologic examination in non-muscle invasive bladder cancer.

OBJECTIVES: The objectives of this study were to determine the prognostic value of expression levels of selected biomarkers and their statistical analysis in relation to survival and standard histopathologic examination and other clinicopathologic variables in non-muscle invasive bladder cancer (NMIBC). BACKGROUND: Worldwide, bladder cancer is a frequent malignant disease with rising incidence. Characteristic invasiveness and high recurrence rates call for more diagnostic methods to obtain more accurate information. Prognosis is affected by a significant interpersonal variability of the disease. For this reason, constant search for alternative and better diagnostic methods is essential. METHODS: We analysed cancer tissue from patients with Ta and T1 bladder cancer. E-cadherin and Ki-67 expression levels were analysed using immunohistochemical staining. The expression levels quantified to a percentual amount were statistically analysed in relation to survival and their frequency distribution in the study group. RESULTS: E-cadherin and Ki-67 expression levels show high association with tumor stage and grade         (p<0.001), in contrast, the association with recurrence has proven insignificant. Patients with non-aberrant biomarker expression levels have much higher survival rates than the cases with aberrant expression. CONCLUSION: Low expression levels of Ki-67 and high expression levels of E-cadherin positively affect survival of patients, whereas aberrant expressions pose poorer prognosis (Tab. 2, Fig. 2, Ref. 33).

Is it possible to estimate urethral mobility based on maximal urethral closure pressure measurements?

OBJECTIVE: Is it possible to estimate urethral mobility based on MUCP measurements? DESIGN: Retrospective study. SETTING: Department of Gynecology and Obstetrics, 1st Medical Faculty, Charles University, General Teaching Hospital, Prague. METHODS: This retrospective study included 567 patients from three prospective studies within years 2002 to 2009. Ultrasound examination was performed in 560 of them and maximal urethral closure pressure (MUCP) values were measured in 507 women. The MUCP was defined as the difference between maximum urethral pressure and bladder pressure. An ultrasound examination was performed using the transperineal approach in accordance with the recommendations of the German Urogynecology Working Group and ICS, IUGA terminology. The mobility was expressed as a distance between the position at rest and at the maximal Valsalva manoeuvre. Data were summarized as mean and median, with SD and quantile range for measures of variability. Either a matched pairs t-test or Wilcoxon test was used for statistical evaluation. RESULTS: Mean MUCP was 47.4 cm H2O (SD 22.2, first quantile 32, third quantile 62). Mean urethral descent was 20.6 mm (SD 8.2, first quantile 14.9, third quantile 25.6 mm). Using regression analysis there was an increase in urethral descent; this difference is statistically significant. For a MUCP increase of 10 cm H2O we could estimate an increase in urethral descent of 1.1 mm. CONCLUSION: We established a statistically significant relationship between urethral descent and MUCP. Unfortunately those differences are not clinically relevant, especially for MUCP over 20 cm H2O. For MUCP below 20 cm H2O low urethral descent is more likely. Clinical use of MUCP as predictor of urethral descent is limited due to the high variability involved.

Biomarkers for determination prostate cancer: implication for diagnosis and prognosis.

Prostate cancer (PCa) belongs to most common cancers and it is the second leading cause of cancer death in men. A genetic predisposition or acquired genetic and epigenetic changes with effect of other factors, such as advanced age, race and environmental factors contribute to PCa development. PCa is a very heterogeneous disease that is characterized by different clinical behavior, from indolent, slow-growing tumors to aggressive, fast-growing tumors with lethal progression. Early diagnostics and identification of PCa type are crucial prerequisites for efficient treatment of patients. Recently, the diagnostics of early stages of PCa is based mostly on evaluation of prostate-specific antigen (PSA) in serum of patients. Men with high levels of PSA undergo biopsy in order to determine histopatological grading of PCa - Gleason scoring which classifies tumors from most to least differentiated as well as staging - determination of the status of their primary tumors, with or without lymph node involvement. The results from this screening diagnosis lead into conventional treatment, including radical prostatectomy and brachytherapy. In case of advanced PCa, conventional treatment continues with androgen deprivation therapy. However, in many cases the cancer recurs. Therefore, the clinicians and researchers are forced to find more precise and sensitive biomarker suitable for PCa diagnostics as well as prognostics and therapy. This paper provides review of current most promising molecular and immunohistochemical biomarkers in PCa diagnosis, prognosis and clinical behavior.

Molecular Biomarkers of Bladder Cancer: A Mini-Review.

Cancers are quite common, but mostly very serious diseases and therefore belong to the most important areas of scientific research activity. Bladder cancer is one of the most common malignancies, it is a heterogeneous disease with significant diagnostic, therapeutic, and prognostic problems. It represents a disease with a variable course and a different response to therapy. The "conventional" prognostic markers used so far cannot reliably predict the natural course of the disease or estimate the tumor response to the chosen type of treatment. Molecular markers can provide us with the opportunity to diagnose a bladder tumor early, identify patients who are at risk of recurrence, or predict how tumors will respond to therapeutic approaches. As a result, diagnostics are found to help clinicians find the best therapeutic options for patients with bladder cancer. In this study, we focused on a brief description of potential molecular markers in bladder tumors in the context of precise diagnostics. Last but not least, we also focused on a new approach to the treatment of cancer using nanomaterials.

Sports activities and cardiovascular system change.

Sports activity is generally considered to be beneficial to health. The World Health Organization (WHO) recommends physical activity as part of a healthy lifestyle. Sports activities significantly affect the cardiovascular system. A number of studies show that they significantly reduce the risk of cardiovascular disease as well as decrease cardiovascular mortality. This review discusses changes in various cardiovascular parameters in athletes - vagotonia/bradycardia, hypertrophy of heart, ECG changes, blood pressure, and variability of cardiovascular parameters. Because of its relationship to the cardiovascular system, VO2max, which is widely used as an indicator of cardiorespiratory fitness, is also discussed. The review concludes with a discussion of reactive oxygen species (ROS) and oxidative stress, particularly in relation to changes in the cardiovascular system in athletes. The review appropriately summarizes the above issues and points out some new implications.

Decellularization techniques of human foreskin for tissue engineering application.

The rapid development of tissue engineering (TE) and regenerative medicine brings an acute need for biocompatible and bioactive biological scaffolds to regenerate or restore damaged tissue. Great attention is focused on the decellularization of tissues or even whole organs, and the subsequent colonization of such decellularized extracellular matrices by recipient cells. The foreskin is an integral, normal part of the external genitalia that forms the anatomical covering of the glans penis and the urinary meatus of all human and non-human primates. It is mucocutaneous tissue that marks the boundary between mucosa and skin. In this work, we compared two innovative decellularization techniques for human foreskins obtained from donors. We compared the efficacy and feasibility of these protocols and the biosafety of prepared acellular dermal matrixes that can serve as a suitable scaffold for TE. The present study confirms the feasibility of foreskin decellularization based on enzymatic or detergent methods. Both techniques conserved the ultrastructure and composition of natural ECM while being DNA-free and non-toxic, making it an excellent scaffold for follow-up research and TE applications.

Monitoring COVID-19 spread in selected Prague's schools based on the presence of SARS-CoV-2 RNA in wastewater.

The COVID-19 pandemic has demanded a broad range of techniques to better monitor its extent. Owing to its consistency, non-invasiveness, and cost effectiveness, wastewater-based epidemiology has emerged as a relevant approach to monitor the pandemic's course. In this work, we analyzed the extent of the COVID-19 pandemic in five primary schools in Prague, the Czech Republic, and how different preventive measures impact the presence of SARS-CoV-2 RNA copy numbers in wastewaters. Copy numbers were measured by reverse transcription-multiplex quantitative real-time PCR. These copy numbers were compared to the number of infected individuals in each school identified through regular clinical tests. Each school had a different monitoring regime and subsequent application of preventive measures to thwart the spread of COVID-19. The schools that constantly identified and swiftly quarantined infected individuals exhibited persistently low amounts of SARS-CoV-2 RNA copies in their wastewaters. In one school, a consistent monitoring of infected individuals, coupled with a delayed action to quarantine, allowed for the estimation of a linear model to predict the number of infected individuals based on the presence of SARS-CoV-2 RNA in the wastewater. The results show the importance of case detection and quarantining to stop the spread of the pandemic and its impact on the presence of SARS-CoV-2 RNA in wastewaters. This work also shows that wastewater-based epidemiological models can be reliably used even in small water catchments, but difficulties arise to fit models due to the nonconstant input of viral particles into the wastewater systems.

Comparative Analysis of Somatic Stem Cells With Emphasis on Osteochondral Tissue Regeneration.

Congenital anomalies, diseases, and injuries may result in osteochondral damage. Recently, a big hope has been given to somatic stem cells (SSCs) which are characterized as undifferentiated cells with an ability of long-term self-renewing and plasticity. They are adherent with a fibroblast-like morphology in vitro and express various surface markers (e.g. CD29, CD73, CD90, and CD105), but they are negative for CD31, CD34, CD45, and HLA-DR. SSCs secrete various bioactive molecules, which are involved in processes of regeneration. The main goal of the present study was the characterization and comparison of biological properties of SSCs obtained from adipose tissue, dental pulp, and urine concerning osteochondral regeneration. SSCs were maintained in an appropriate growth medium up to the third passage and were analyzed by light and electron microscope. The immunophenotype was analyzed by flow cytometry. The kinetics of proliferation was measured by MTT assay. Human Cytokine/Chemokine Multiplex Assay was used, and SSCs secretory profile was measured by Luminex MAGPIX® Instrument. Pellet cultures and a chondrogenic medium were used to induce chondrogenic differentiation. Osteogenic differentiation was induced by the osteogenic medium. Chondrogenic and osteogenic differentiation was analyzed by real-time PCR. SSCs had similar fibroblast-like morphology. They have similar kinetics of proliferation. SSCs shared the expression CD29, CD44, CD73, CD90, and CD105. They lack expression of CD29 and CD34. SSCs secerned similar levels of IL10 and IL18 while differing in IFN-gamma, IL6, IL8, MCP-1, and RANTES production. SSCs possess a similar capacity for chondrogenic differentiation but slightly differ in osteogenic differentiation. In conclusion, it can be emphasized that SSCs from adipose tissue, dental pulp, and urine share the majority of cellular characteristics typical for SSCs and have great potential to be used in osteochondral tissue regeneration.

Effects of peroral hormonal contraception on cardiovascular system: analysis of selected cardiovascular parameters in an adolescent cohort; a pilot project.

Oral contraceptive pills (OCPs) have some strong advantages over more traditional types of contraception, including their consistently high contraceptive effect as well as multiple additional positive side effects. OCPs went through decades of intense pharmaceutical development and current formulas are well optimized - however, a handful of their negative side effects remain, including some that affect cardiovascular system, for example higher risk of hypertension, venous thromboembolism and increased arterial stiffness. The gold standard for arterial stiffness assessment is currently applanation tonometry, a method that relies on arterial pulse wave velocity measurement (PWV). Another possible method for arterial stiffness measurement is the use of the VaSera device, which measures cardio-ankle vascular index (CAVI). The aim of this study was to discover the effect of OCPs use on selected cardiovascular parameters related to arterial stiffness. We measured these cardiovascular parameters in the OCPs using group (OCP) and in the control group (CTRL) using applanation tonometer Sphygmocor and the VaSera device. Comparison of the data from both groups showed us significantly increased diastolic blood pressure (DBP) and carotid-radial pulse wave velocity (crPWV) as well as significantly lower subendocardial viability index (SVI) in the OCP. These results imply a negative effect of hormonal contraceptives on the cardiovascular system with most of the negative changes affecting the peripheral arteries. Despite this evidence supporting the hypothesis of OCPs having a negative effect on cardiovascular health, further research is necessary.

Mineral water Vincentka and its influence on mucosal ulcers.

Gastropathy is one of the most common diseases of the human gastrointestinal tract. Apart from its consequences in the stomach, it is also manifested in other parts of the digestive tract, particularly in the duodenum. The aim of this pilot study was to verify on animal model the empirically observed alleviation of gastropathy symptoms in patients who underwent a drinking treatment of Vincentka natural mineral water during their spa treatment. Sixteen male Wistar rats were included in the study. The animals were randomly divided into two groups: experimental group (E; n=8) and control group (C; n=8). The experimental protocol consisted of three phases: (1) handling phase (7 days); (2) mineral water (E)/tap water (C) administration (7 days); (3) acute gastritis induction (1 day). Twenty-four hours after the induction of acute gastritis, the animals were sacrificed. The collected tissues (stomach and duodenum) and blood were examined by standard histological microscopy, and by immunohistochemical and biochemical methods. Histopathological analysis revealed significantly reduced damage to the gastric mucosa in the experimental group. Significantly different values of blood plasma antioxidant capacity, oxidative stress parameters and blood plasma biochemical parameters were also found. Based on these results, we conclude that the mineral water Vincentka has a positive impact on development and symptoms of acute gastric ulcers.

CT evaluated sarcopenia signals: Shorter survival for small cell lung cancer patients.

Sarcopenia is an independent risk factor for morbidity and mortality in patients suffering from small cell lung cancer (SCLC), however, a universal indicator of sarcopenia usable in clinical practice is still missing. A novel indicator for describing the severity of cancer could be helpful in tailoring the anti-tumor therapy. The aim of this study was to evaluate the computed tomography (CT) scans of total muscle area and radiation attenuation in patients suffering from small cell lung cancer. We used staging CT scans performed at the time of diagnosis to measure total muscle area (TMA) and average psoas density (PD) at level of the 3rd lumbar vertebra. TMA and PD were statistically evaluated in association with overall survival and disease staging. We used Mann-Whitney test and Spearman´s correlation coefficient for statistical testing and p-value under 0.05 was considered statistically significant. Retrospectively we examined 47 patients suffering from SCLC (mean age 65.05+/-7.3 years, BMI 23.97+/-4.4 kg/m2, BSA 1.77+/-0.2 m2, 30-day mortality was 4.3 % with 10 months median survival). As sarcopenia was pointed TMA under 55 and 39 cm2/m2 for men and women respectively. The sarcopenic patients had significantly shorter median survival (7 vs. 11 months, p=0.05). We observed a significant relationship between survival and performance status (Spearman´s correlation, R=-0.39, p=0.05). The patients were divided into two groups according to the extensive (ED, n=34) or limited (LD, n=13) form of the disease. We observed significant difference in PD (42.49+/-6.1 vs. 47.67+/-4.5 HU, p=0.006) between ED vs. LD groups.

Reproducibility of blood pressure and inter-beat interval variability in man.

Increased blood pressure variability (BPV) and decreased inter-beat interval (heart rate, respectively) variability (IBIV, HRV respectively) are associated with cardiovascular disorders. The aim of this study was to evaluate the reproducibility of BPV and IBIV (HRV) in young healthy individuals. Blood pressure and inter-beat intervals (instantaneous values of heart rate, respectively) were recorded beat-to-beat at rest (5 min, Finapres, breathing at 0.33 Hz) in 152 subjects (19-24 years) 3 times in periods of one week. Systolic (SBPV(0.1r)/SBPV(0.1a)) and diastolic (DBPV(0.1r)/DBPV(0.1a)) blood pressure variability in relative (r.u.) and absolute (mmHg(2)/Hz) units and inter-beat interval (IBIV(0.1r)/IBIV(0.1a)), or heart rate (HRV(0.1r)/HRV(0.1a)) variability in relative (r.u.) and absolute (ms(2)/Hz, resp. mHz(2)) units were determined by the spectral method as spectral power at the frequency of 0.1 Hz and 0.33 Hz (SBPV(0.33r)/SBPV(0.33a), DBPV(0.33r)/DBPV(0.33a), IBIV(0.33r)/IBIV(0.33a), HRV(0.33r)/HRV(0.33a)). All indices of BPV and IBIV (resp. HRV) revealed a lower intraindividual than interindividual variability (ANOVA; p<0.001). The mean values of all indices in each subject significantly correlated with distribution of individual values in the same subject (Pearson's correlation coefficient; p<0.001). Blood pressure and inter-beat interval (heart rate) variability is an individual characteristic feature.

Logit and fuzzy models in data analysis: estimation of risk in cardiac patients.

The aim of this study was a comparison of risk stratification for death in patients after myocardial infarction (MI) and of risk stratification for malignant arrhythmias in patients with implantable cardioverter-defibrillator (ICD). The individual risk factors and more complex approaches were used, which take into account that a borderline between a risky and non-risky value of each predictor is not clear-cut (fuzzification of a critical value) and that individual risk factors have different weight (area under receiver operating curve - AUC or Sommers' D - Dxy). The risk factors were baroreflex sensitivity, ejection fraction and the number of ventricular premature complexes/hour on Holter monitoring. Those factors were evaluated separately and they were involved into logit model and fuzzy models (Fuzzy, Fuzzy-AUC, and Fuzzy-Dxy). Two groups of patients were examined: a) 308 patients 7-21 days after MI (23 patients died within period of 24 month); b) 53 patients with left ventricular dysfunction examined before implantation of ICD (7 patients with malignant arrhythmia and electric discharge within 11 month after implantation). Our results obtained in MI patients demonstrated that the application of logit and fuzzy models was superior over the risk stratification based on algorithm where the decision making is dependent on one parameter. In patients with implanted defibrillator only logit method yielded statistically significant result, but its reliability was doubtful because all other tests were statistically insignificant. We recommend evaluating the data not only by tests based on logit model but also by tests based on fuzzy models.

Association of A1166C polymorphism in AT(1) receptor gene with baroreflex sensitivity.

The aim of this study was to evaluate the association of A1166C polymorphism in angiotensin II type 1 receptor (AT(1)R) gene with baroreflex sensitivity (BRS in ms/mm Hg; BRSf in mHz/mm Hg) in man. BRS and BRSf were determined by a spectral method in 135 subjects (19-26 years) at a frequency of 0.1 Hz. Genotypes were detected by means of polymerase chain reaction and restriction analysis using enzyme DdeI. We compared BRS and BRSf among genotypes of this polymorphism. The frequency of genotypes of AT(1)R A1166C polymorphism was: 45.9 % (AA, n=62), 45.9 % (AC, n=62), 8.2 % (CC, n=11). Differences in BRS (p<0.05) and BRSf (p<0.01) among genotypes of this single nucleotide polymorphism were found (Kruskal-Wallis: BRS - AA: 7.9+/-3.3, AC: 8.6+/-3.6, CC: 5.9+/-2.3 ms/mm Hg; BRSf - AA: 12.0+/-4.0, AC: 12.0+/-5.0, CC: 8.0+/-3.0 mHz/mm Hg). Compared to carriers of other genotypes (AA+AC) the homozygotes with the less frequent allele (CC) showed significantly lower BRSf (Mann-Whitney: BRSf - AA+AC: 12.0+/-4.0, CC: 8.0+/-3.0 mHz/mm Hg; p<0.01) and borderline lower BRS (BRS - AA+AC: 8.2+/-3.5, CC: 5.9+/-2.5 ms/mm Hg; p=0.07). We found a significant association of A1166C polymorphism in AT(1) receptor gene with baroreflex sensitivity. Homozygosity for the less frequent allele was associated with decreased baroreflex sensitivity.

Comparison of baroreflex sensitivity determined by cross-spectral analysis at respiratory and 0.1 Hz frequencies in man.

Non-invasive methods of determination of baroreflex sensitivity (BRS, ms/mmHg) are based on beat-to-beat systolic blood pressure and inter-beat interval recording. Sequential methods and spectral methods at spontaneous breathing include transient superposition of breathing and 0.1 Hz rhythms. Previously, a cross-spectral method of analysis was used, at constant breathing rate using a metronome set at 0.33 Hz, enabling separate determination of BRS at 0.1 Hz (BRS(0.1Hz)) and respiratory rhythms (BRS(0.33Hz)). The aim of the present study was to evaluate the role of breathing in the spectral method of BRS determination with respect to age and hypertension. Such information would be important in evaluation of BRS at pathological conditions associated with extremely low BRS levels. Blood pressure was recorded by Finapres (5 minutes, controlled breathing at 0.33 Hz) in 118 healthy young subjects (YS: mean age 21.0+/-1.3 years), 26 hypertensive patients (HT: mean age 48.6+/-10.3 years) with 26 age-matched controls (CHT: mean age 46.3+/-8.6 years). A comparison of BRS(0.1Hz) and BRS(0.33Hz) was made. Statistically significant correlations were found between BRS(0.1Hz) and BRS(0.33Hz) in all groups: YS: r=0.52, p<0.01, HT: r=0.47, p<0.05, and CHT: r=0.70, p<0.01. The regression equations indicated the existence of a breathing-dependent component unrelated to BRS (YS: BRS(0.33Hz)=2.63+1.14*BRS(0.1Hz); HT: BRS(0.33Hz)=3.19+0.91*BRS(0.1Hz); and CHT: BRS(0.33Hz)=1.88+ +1.01*BRS(0.1Hz); differences between the slopes and the slope of identity line were insignificant). The ratios of BRS(0.1Hz) to BRS(0.33Hz) were significantly lower than 1 (p<0.01) in all groups (YS: 0.876+/-0.419, HT: 0.628+/-0.278, and CHT: 0.782+/-0.260). Thus, BRS evaluated at the breathing rate overestimates the real baroreflex sensitivity. This is more pronounced at low values of BRS, which is more important in patients with pathologic low BRS. For diagnostic purposes we recommend the evaluation of BRS at the frequency of 0.1 Hz using metronome-controlled breathing at a frequency that is substantially higher than 0.1 Hz and is not a multiple of 0.1 Hz to eliminate respiratory baroreflex-non-related influence and resonance effect on heart rate fluctuations.

Anthracycline therapy and 24-hour blood-pressure profile in long-term survivors of childhood cancer.

In our previous studies, a decreased blood pressure was reported in children treated by anthracycline (AC). The aim of this study was to assess the long-term effects of AC anticancer therapy in 45 subjects aged 13-22 years by repeated 24-hour Holter monitoring of blood pressure. Sixty four aged-matched subjects served as controls. The differences between mean values of systolic (SBP) and diastolic blood pressure (DBP) in each hour of both groups were evaluated by Mann-Whitney test. Also the parameters of the least-squares fit of the sinusoidal curve in each subject were estimated (M - mesor, midline-estimating, a mean value of sinusoidal curve corresponds to 24-hours mean pressure; A - amplitude, double amplitude corresponds to night-day difference; Acr - acrophase is a time of maximal value of a sinusoidal curve). SBP and DBP was significantly lower only during night hours in anthracycline patients 19-22 years old. Also M was lower in this age subgroup of patients comparing to age matched controls (SBP: 112+/-6 mm Hg versus 117+/-7 mm Hg, p<0.05; DBP: 67+/-3 mm Hg versus 69+/-6 mm Hg, p<0.05), A was not different, Acr in patients was shifted one hour earlier (SBP: 2.4 p.m. versus 3.6 p.m., p<0.05; DBP: 2.1 p.m. versus 3.3 p.m., p<0.01). This corresponds to the shift of the morning blood-pressure increase seen on 24-hours blood pressure profiles. M correlated with age in controls (SBP: r=0.374, p<0.01; regression coefficient b=1.34 mm Hg/1 year; DBP: r=0.365, p<0.01; b=0.95 mm Hg/1 year), but not in patients (SBP: r=0.182, DBP: r=0.064). A and Acr were age-independent in all subjects. It is concluded that blood pressure in 19-22 years old AC patients is lower during night hours, the age-dependent increase of blood pressure seen in healthy controls between 13 and 22 years of age does not occur in patients. This finding is consistent with the long-lasting impairment of the sympathetic nervous system caused by anthracyclines.

Variability of peripheral pulse wave velocity in patients with diabetes mellitus type 2 during orthostatic challenge.

Diabetes mellitus 2 (DM2) is the seventh cause of death worldwide. One of the reasons is late diagnosis of vascular damage. Pulse wave velocity (PWV) has become an independent marker of arterial stiffness and cardiovascular risk. Moreover, the previous studies have shown the importance of beat-to-beat PWV measurement due to its variability among the heart cycle. However, variability of PWV (PWVv) of the whole body hasn't been examined yet. We have studied a group of DM II and heathy volunteers, to investigate the beat-to-beat mean PWV (PWVm) and PWVv in the different body positions. PWV of left lower and upper extremities were measured in DM2 (7 m/8 f, age 68+/-10 years, BP 158/90+/-19/9 mm Hg) and healthy controls (5 m/6 f, age 23+/-2 years, BP 117/76+/-9/5 mm Hg). Volunteers were lying in the resting position and of head-up-tilt in 45° (HUT) for 6 min. PWVv was evaluated as a mean power spectrum in the frequency bands LF and HF (0.04-0.15 Hz, 0.15-0.5 Hz). Resting PWVm of upper extremity was higher in DM2. HUT increased lower extremity PWVm only in DM2. Extremities PWVm ratio was significantly lower in DM2 during HUT compared to controls. LF and HF PWVv had the same response to HUT. Resting PWVv was higher in DM2. Lower extremity PWVv increased during HUT in both groups. PWVm and PWVv in DM2 differed between extremities and were significantly influenced by postural changes due to hydrostatic pressure. Increased resting PWVm and PWVv in DM2 is a marker of increased arterial stiffness.

Biomarkers of exposure to tobacco smoke and environmental pollutants in mothers and their transplacental transfer to the foetus. Part II. Oxidative damage.

Oxidative damage to macromolecules may have numerous negative health consequences. We measured oxidative damage to DNA, proteins and lipids in 80 newborns and 79 mothers, analyzed the effect of mother's tobacco smoke exposure on oxidative stress, and assessed correlations between oxidative stress markers and bulky and PAH (polycyclic aromatic hydrocarbons)-specific DNA adducts. Mean levels (+/-S.D.) of 8-oxodeoxyguanosine (8-oxodG) per 10(5) dG in the placenta were 2.85+/-0.78; we did not see a difference between 8-oxodG levels in newborns born to mothers exposed and unexposed to tobacco smoke. Protein carbonyl levels, a marker of protein oxidation, were comparable in the umbilical cord and in maternal venous blood plasma (17.4+/-3.2 and 17.6+/-4.2nmol/ml plasma in newborns and mothers, respectively, p=0.66). Lipid peroxidation measured as levels of 15-F(2t)-isoprostane (15-F(2t)-IsoP) in plasma was significantly higher in newborns than in mothers (362+/-129 and 252+/-130pg/ml in newborns and mothers, respectively, p<0.001). We did not find any effect of tobacco smoke exposure on either biomarker in any group. Levels of both protein carbonyls and 15-F(2t)-IsoP in cord blood significantly correlated with those in maternal plasma (p<0.001). 8-oxodG levels positively correlated with plasma carbonyls in cord plasma, as well as with cotinine levels (marker of tobacco smoke exposure) in maternal plasma. 8-oxodG levels also correlated with bulky DNA adducts in lymphocyte DNA of newborns and mothers and with PAH-DNA adducts in the placenta. Our results showed higher lipid peroxidation in newborns than in mothers, close correlation of analyzed oxidative stress markers between newborns and mothers, and a relationship between oxidative stress and induction of DNA adducts.

Biomarkers of exposure to tobacco smoke and environmental pollutants in mothers and their transplacental transfer to the foetus. Part I: bulky DNA adducts.

(32)P-postlabelling and PAH-ELISA using the antiserum #29 were employed to analyze DNA adducts in venous and umbilical cord blood and the placenta of 79 mothers giving birth to 80 living babies in Prague (Czech Republic). Ambient air exposure was measured by stationary measurements of basic air pollutants (PM2.5, c-PAHs) during the entire pregnancy. Tobacco smoke exposure was assessed by questionnaire data and by plasma cotinine levels. The total DNA adduct levels in the lymphocytes of mothers and newborns were elevated by 30-40% (p<0.001) compared with the placenta. B[a]P-like DNA adduct (adduct with the identical chromatographic mobility on TLC as major BPDE derived DNA adduct) levels were elevated in the blood of mothers compared with the placenta and the blood of newborns (p<0.05 and p<0.01). In tobacco smoke-exposed mothers, higher DNA adduct levels in the blood of mothers and newborns compared with the placenta were found (p<0.001), whereas the total and B[a]P-like adduct levels were comparable in the blood of mothers and newborns. B[a]P-like adducts were elevated in the blood of mothers unexposed to tobacco smoke compared with that of corresponding newborns and the placenta (p<0.01). Total and B[a]P-like DNA adducts were increased in the placenta of tobacco smoke-exposed compared with unexposed mothers (p<0.001 and p<0.01). In lymphocytes of tobacco smoke-exposed mothers, the comparison of total adduct levels (1.18+/-0.67 vs. 0.92+/-0.28) and B[a]P-like DNA adducts (0.22+/-0.12 adducts/10(8) nucleotides vs. 0.15+/-0.06 adducts/10(8) nucleotides) with newborns indicated a 30-40% increase of adducts in mothers. Almost equal PAH-DNA adduct levels were detected by anti-BPDE-DNA ELISA in the placenta of tobacco smoke-exposed and -unexposed mothers. Our results suggest a protective effect of the placental barrier against the genotoxic effect of some tobacco smoke components between the circulation of mother and child. We found a correlation between adduct levels in the blood of mothers and newborns.

Status of nutrition and cardiovascular system in children from the south Moravian region of the Czech Republic: a pilot study.

Nutritional status, its assessment and its influence on numerous diseases is currently still being discussed. The aim of this study was to determine the current state of nutrition by various research methods in school children. Also, to verify the accuracy of body mass index (BMI) determination in school environment and to compare the nutritional status in two different types of school. We used a quantitative questionnaire method in 64 children from schools in the South Moravian Region. We have verified the weight and height measurement in the same group by sophisticated instruments. We have determined the basic parameters of the cardiovascular system (non-invasive continuously blood pressure recording; mutual spectral analysis for estimation of baroreflex sensitivity; applanation tonometry and cardiac polygraphy for arterial stiffness evaluation). The indicative questionnaire method encountered a problem with the weight of almost 40 % of the population approached - both obesity (14.3 %) and malnutrition (25.2 %). Cardiovascular parameters were in physiological range for the given age categories. We found increased values in BMI, % of body fat and heart rate in children from countryside type of school, respectively. We concluded that obesity/malnutrition are both common phenomena in the children population in the Czech Republic.