Physical Effects of Radiation Modification of Biodegradable Xylitol-Based Materials Synthesized Using a Combination of Different Monomers.

There is a possibility of obtaining xylitol-based elastomers sharing common characteristics of biodegradability, thermal stability, and elastomeric behavior by using monomers with different chain-lengths. Therefore, we have synthesized eight elastomers using a combination of four different diols (ethanediol, 1.3-propanediol, 1.4-buanediol, and 1.5-pentanediol) and two different dicarboxylic acids (succinic acid and adipic acid). The obtained materials were further modified by performing e-beam treatment with a dose of 100 kGy. Materials both before and after radiation modification were tested by DSC, DMTA, TGA, tensile tests, gel fraction determination, hydrolytic and enzymatic degradation tests, 1H NMR and 13C NMR and FTIR.

Association between a urinary biomarker for exposure to PAH and blood level of the acute phase protein serum amyloid A in coke oven workers.

BACKGROUND: Coke oven workers are exposed to both free and particle bound PAH. Through this exposure, the workers may be at increased risk of cardiovascular diseases. Systemic levels of acute phase response proteins have been linked to cardiovascular disease in epidemiological studies, suggesting it as a marker of these conditions. The aim of this study was to assess whether there was association between PAH exposure and the blood level of the acute phase inflammatory response marker serum amyloid A (SAA) in coke oven workers. METHODS: A total of 87 male Polish coke oven workers from two different plants comprised the study population. Exposure was assessed by means of the individual post-shift urinary excretion of 1-hydroxypyrene, as internal dose of short-term PAH exposure, and by anti-benzo[a]pyrene diolepoxide (anti-B[a]PDE)-DNA), as a biomarker of long-term PAH exposure. Blood levels of acute phase proteins SAA and CRP were measured by immunoassay. C-reactive protein (CRP) levels were included to adjust for baseline levels of SAA. RESULTS: Multiple linear regression showed that the major determinants of increased SAA levels were urinary 1-hydroxypyrene (beta = 0.56, p = 0.030) and serum CRP levels (beta = 7.08; p < 0.0001) whereas anti-B[a]PDE-DNA, the GSTM1 detoxifying genotype, diet, and smoking were not associated with SAA levels. CONCLUSIONS: Urinary 1-hydroxypyrene as biomarker of short-term PAH exposure and serum levels of CRP were predictive of serum levels of SAA in coke oven workers. Our data suggest that exposure of coke oven workers to PAH can lead to increased systemic acute response and therefore potentially increased risk of cardiovascular disease.

Monitoring the Transcriptional Activity of Human Endogenous Retroviral HERV-W Family Using PNA Strand Invasion into Double-Stranded DNA.

In the presented assay, we elaborated a method for distinguishing sequences that are genetically closely related to each other. This is particularly important in a situation where a fine balance of the allele abundance is a point of research interest. We developed a peptide nucleic acid (PNA) strand invasion technique for the differentiation between multiple sclerosis-associated retrovirus (MSRV) and ERVWE1 sequences, both molecularly similar, belonging to the human endogenous retrovirus HERV-W family. We have found that this method may support the PCR technique in screening for minor alleles which, in certain conditions, may be undetected by the standard PCR technique. We performed the analysis of different ERVWE1 and MSRV template mixtures ranging from 0 to 100% of ERVWE1 in the studied samples, finding the linear correlation between template composition and signal intensity of final reaction products. Using the PNA strand invasion assay, we were able to estimate the relative ERVWE1 expression level in human specimens such as U-87 MG, normal human astrocytes cell lines and placental tissue. The results remained in concordance with those obtained by semi-quantitative or quantitative PCR.

The analysis of blood lead levels changeability over the 5-year observation in workers occupationally exposed to lead.

The aim of the present study was to compare a group of workers with stable lead levels with a group of workers with fluctuating lead levels in terms of selected hematological, biochemical, and immunological parameters. The examined group included male workers occupationally exposed to lead. Blood lead (PbB) levels were measured every 3 months during the 5-year observation. Based on standard deviation of mean PbB levels, the examined population was divided into two groups: low level of fluctuation (L-SD) and high level of fluctuation (H-SD) groups. The mean and maximal PbB levels were significantly higher in the H-SD group than in the L-SD group by 9 and 22%, respectively. At the same time, the maximal level of zinc protoporphyrin (ZPP) and standard deviation of mean ZPP level were higher in the H-SD group by 29 and 55%, respectively. The maximal level of hemoglobin and white blood cell (WBC) count as well as standard deviation of the mean hemoglobin level and WBC count were higher in the H-SD group by 2, 8, 58, and 24%, respectively. The expression of nuclear factor kappa-B1 gene and telomerase reverse transcriptase gene was significantly greater in the H-SD group than in the L-SD group by 11 and 28%, respectively. Workers occupationally exposed to lead do not represent a homogenous population. Some present stable lead levels, whereas others have fluctuating lead levels. These fluctuations are related to secondary changes in ZPP and hemoglobin levels as well as WBC count.

Glutathione, glutathione-related enzymes, and oxidative stress in individuals with subacute occupational exposure to lead.

The aim of the study was to investigate the influence of subacute exposure to lead on the glutathione-related antioxidant defense and oxidative stress parameters in 36 males occupationally exposed to lead for 40±3.2days. Blood lead level in the examined population increased significantly by 359% due to lead exposure. Simultaneously, erythrocyte glutathione level decreased by 16%, whereas the activity of glutathione-6-phosphate dehydrogenase in erythrocytes and leukocytes decreased by 28% and 10%, respectively. Similarly, the activity of glutathione-S-transferase in erythrocytes decreased by 45%. However, the activity of glutathione reductase in erythrocytes and leukocytes increased by 26% and 6%, respectively, whereas the total oxidant status value in leukocytes increased by 37%. Subacute exposure to lead results in glutathione pool depletion and accumulation of lipid peroxidation products; however, it does not cause DNA damage. Besides, subacute exposure to lead modifies the activity of glutathione-related enzymes.

Telomere length, telomerase expression, and oxidative stress in lead smelters.

The negative health effects caused by lead (Pb) exposure are widely recognized; however, the molecular mechanisms remain unknown. The aim of this study was to assess the effect of occupational Pb exposure on telomere length and to investigate the potential mechanisms leading to telomere shortening. A cohort of 334 male Pb smelters (exposed group) and 60 age-adjusted males unexposed to Pb (control group) were examined. Assessments of relative telomere length (rTL) and telomerase reverse transcriptase (TERT) gene expression were performed using quantitative real-time polymerase chain reactions. Assessments of whole blood Pb (B-Pb) and whole blood cadmium (B-Cd) concentrations and serum selenium concentration (S-Se) were performed using graphite furnace atomic absorption spectrometry. We analyzed total oxidation status (TOS), lipid hydroperoxides (LHPs), malonylodialdehyde levels in serum (MDA) and in erythrocyte hemolysates (MDA-hgb), and 8-hydroxy-deoxy-guanosine (8-OHdG). The Pb-exposed group had higher B-Pb values and shorter rTL than the control group. The arithmetic mean values calculated for B-Pb were 33 µg/dL versus 2.2 µg/dL (p < 0.0001), and the rTL values were 0.928 and 1.126 relative units (p = 0.001), respectively, for the Pb-exposed and control groups. The rTL was found to gradually shorten in response to the increasing levels of Pb exposure. The Pb-exposed group also demonstrated a higher level of oxidative stress than the control group, which was indicated by increased TOS and MDA-hgb values. rTL was negatively associated with parameters that indicated increased oxidative stress, including TOS (Spearman's rank coefficient (rS) = -0.16; p < 0.01) and MDA-hgb (rS = -0.17; p < 0.001). No correlations were found between rTL and B-Cd and S-Se or smoking and MDA and LHP levels. Univariate analysis indicated that B-Pb was associated with decreased rTL (ß =-0.0041; p = 0.0063) and that the association between B-Pb and rTL remained significant, even when adjusting for age (ß = -0.0041; p = 0.0065) and in multivariable-adjusted model (ß = -0.0042; p = 0.0063). In conclusion, occupational Pb exposure resulted in decreased rTL and may represent a mechanism that contributes to Pb-related diseases.

Telomere length in children environmentally exposed to low-to-moderate levels of lead.

Shorter relative telomere length in peripheral blood is a risk marker for some types of cancers and cardiovascular diseases. Several environmental hazards appear to shorten telomeres, and this shortening may predispose individuals to disease. The aim of the present cross-sectional study was to assess the effect of environmental exposure to lead on relative telomere length (rTL) in children. A cohort of 99 8-year-old children was enrolled from 2007-2010. Blood lead concentrations (B-Pb) were measured by graphite furnace atomic absorption spectrometry, and blood rTL was measured by quantitative PCR. The geometric mean of B-Pb was 3.28 µg/dl (range: 0.90-14.2), and the geometric mean of rTL was 1.08 (range: 0.49-2.09). B-Pb was significantly inversely associated with rTL in the children (rS = -0.25, p = 0.013; in further analyses both log-transformed-univariate regression analysis ß = -0.13, p = 0.026, and R(2)adj 4%; and ß = -0.12, p = 0.056 when adjusting for mothers' smoking during pregnancy, Apgar score, mother's and father's ages at delivery, sex and mother's education, R(2)adj 12%, p = 0.011). The effect of lead remained significant in children without prenatal tobacco exposure (N = 87, rS = -0.24, p = 0.024; in further analyses, ß = -0.13, p = 0.029, and R(2)adj 4%). rTL was not affected by sex, the concentrations of other elements in the blood (i.e., cadmium and selenium concentrations), or oxidative injury parameters (total antioxidant status, 8-hydroxydeoxyguanosine and thiobarbituric acid-reactive substances). Lead exposure in childhood appears to be associated with shorter telomeres, which might contribute to diseases, such as cardiovascular disease. The inverse association between blood lead level and the telomeres in children emphasizes the importance of further reducing lead levels in the environment.

[Air quality vs. morbidity to lung cancer in selected provinces and localities of the Silesian region]. / Jakosc powietrza atmosferycznego a zapadalnosc na nowotwory pluc w wybranych miejscowosciach i powiatach województwa slaskiego.

The objective of the study was analysis of the relationship between the quality of ambient air and icidence of lung cancer based on the results of measurements of selected indicator substances and epidemiological data from the localities/provinces in the Silesian Region. The levels of pyrene, benzoanthracene, benzopyrene and dibenzo(a,h)anthracene were analysed, as well as the concentrations of PM10 fractions sampled on glass fibre filters at sampling stations in 5 localities and 8 provinces in the Silesian Region. The classification of morbidity to lung cancer for the localities and provinces in the study was presented based on the data from the Regional Silesian Cancer Registry. In the group of males a relationship was observed between an increased morbidity to lung cancer and an increasing concentration of pyrene and PM10 respirable dust fraction in ambient air. The preliminary analyses confirmed the strong effect of the quality of ambient air on incidence of lung cancer in the Silesian Region.

Plasma levels of soluble tumor necrosis factor-alpha receptors are related to total and LDL-cholesterol in lean, but not in obese subjects.

BACKGROUND: Tumor necrosis factor-alpha (TNFalpha) is a mediator of insulin resistance. Plasma levels of soluble TNFalpha receptors (sTNFR1 and sTNFR2) probably reflect paracrine action of the cytokine. TNFalpha is also a regulator of lipid metabolism, however, data about impact of obesity on the relationships between TNFalpha and plasma lipids remain controversial. AIM: The purpose of the present study was to examine the associations of TNFalpha system with plasma lipids in lean and obese subjects with normal glucose metabolism. METHODS: We examined 63 subjects, 33 lean (BMI<25 kg x m(-2)) and 30 with marked overweight or obesity (BMI>27.8 kg x m(-2)). Anthropometric and biochemical parameters were measured. Oral glucose tolerance test and euglycemic hyperinsulinemic clamp were also performed. RESULTS: Obese subjects were markedly more insulin resistant and had higher levels of both TNFalpha receptors. Total (TC) and LDL-cholesterol (LDL-C), triglycerides (TG) and non-esterified fatty acids (NEFA) were also higher in the obese group. In obese subjects, both receptors were significantly related to TG and HDL-cholesterol (HDL-C), while sTNFR2 was also associated with NEFA. All those correlations disappeared after controlling for insulin sensitivity. In lean subjects, both receptors were related to TC, HDL-C and LDL-C. In that group, sTNFR1 predicted values of all those parameters independently of BMI, plasma glucose and insulin, and insulin sensitivity. CONCLUSION: We conclude that TNFalpha receptors are associated with plasma lipids in different way in lean and in obese subjects. TNFalpha system is probably important in determining cholesterol levels in lean subjects, while in obese this effect might be masked by other metabolic abnormalities.

The objective of psychological evaluation in the process of qualifying candidates for bariatric surgery.

Psychosocial and behavioral variables play an important role in both the development and treatment of obesity. Therefore, in the process of qualifying the patient for bariatric surgery, it is necessary to professionally evaluate his/her psychological state. Such evaluation is very helpful in the identification of factors potentially disturbing the effectiveness of the treatment. Clinical interviews with a group of 80 patients were conducted by a psychologist in the pre- and post-surgical period. The qualitative analysis of the interviews led to the identification of the major elements which should become the object of psychological evaluation in the process of qualifying patients for bariatric surgery. Conducting a clinical interview comprising these elements allows one to evaluate their potential influence on the process of surgical treatment of obesity and to provide optimal psychological support for the patient before and after the surgery.

[Individual sensitivity to the mutagenic agents in patients with larynx cancer]. / Ocena wrazliwosci pacjentów z rakiem krtani na czynniki mutagenne.

Patients with different cancers, induced mostly by numerous mutagenic factors, present increased genetic susceptibility to mutagenic agents known as "hidden chromosomal instability". This type of genetic instability can be detected in vitro after treating chromosomes with clastogenic substances, for example by using "bleomycine test". The purpouse of our study was to evaluate a hidden chromosome instability in patients with squamous cell carcinoma of larynx (SCCL) and to establish correlations between genetic results and both histological grade of the tumor and clinical progression of disease. Cytogenetic analysis of 126 of patients diagnosed with SCCL and 98 of controls was performed in vitro on peripheral blood lymphocytes. The analysis of sensitivity to bleomycine of larynx cancer patients in relation to histological grade of the tumor proved, that increased numbers of chromosome breaks as well as and percentage of aberrant metaphases are correlated with the tumor grading. Mean number of chromosome breaks per cell (b/c) in patients with larynx cancer was 1,01 (+/- 0.43), while in the control group was 0.74 (+/- 0.29) per cell (chi2 p < 0.001). Percentage of aberrant metaphases (% am) in patients with SCCL was 42.18 (+/- 11.61) and 36.05 (+/- 10.22) in the control (chi2 p < 0.001). The group of hypersensitive patients (b/c > 1) consisted of 51.5% percent of larynx cancer patients, while in the control, hypersensitivity occurred only in 20.4% of subjects (chi2 p < 0.001). Possible chromosome instability (0.8 < b/c < 1) was found 11.9% patients with SCCL and in 20.4% of controls (not statistically significant). Increased sensitivity to bleomycine in patients with SCCL in comparison to the control group was found. Most sensitive to bleomycine was the group of patients diagnosed with SCCL graded G2 (Scheffe's test p < 0.05)

Correlation among loss of heterozygosity, promoter methylation and protein expression of MLH1 in larynx cancer.

Extensive molecular studies in development of the squamous cell carcinoma of larynx (SCCL) indicated the involvement of a variety of genes including the MLH1. To search for possible mechanism leading to MLH1 silencing in SCCL we studied LOH and promoter methylation in a homogeneous set of 62 larynx cancers. Then we evaluated immunohistochemically the MLH1 expression for 51 tumor specimens. Further, the results were correlated with microsatellite instability and subsequently with the clinical course of the disease. LOH at the MLH1 locus and aberrant methylation of its promoter were found in 47.9 and in 22.6% of tumors, respectively. A decreased expression was observed in 27.5% of the cases. MSI analysis of tumor DNA showed a microsatellite stable phenotype in 59 cases (95.2%). From our study it can be concluded that: i) molecular alterations of MLH1 play an important role in SSCL development, ii) both LOH and aberrant methylation contribute to the MLH1 inactivation in SCCL and are associated with a less advanced stage of differentiation of larynx tumors, iii) MLH1 inactivation does not lead to MSI in larynx cancer and MSI may not contribute to the development of SCCL.

Analysis of adaptive response to bleomycin and mitomycin C.

Genetic instability resulting from the disturbances in various mechanisms of DNA-repair is the characteristic feature of cancer cells. One of the possibilities to evaluate the effectiveness of DNA-repair system is the adaptive response (AR) analysis. The AR is a phenomenon by which cells exposed to low, non-genotoxic doses of a mutagen become significantly resistant to a subsequent higher dose of the same or another genotoxic agent. Generally, it is postulated that AR is related to a reduction of damage by the induction of free radical detoxification and/or DNA-repair systems. The existence of various DNA-repair mechanisms poses the question whether there are differences in AR induced by chemicals causing DNA-damage that requires different pathways for its repair. In this paper we present the study on the AR induced by two chemical mutagens, bleomycin (BLM) and mitomycin C (MMC), which differ in their action on DNA. BLM is a radiomimetic agent causing mainly single-strand breaks (SSB) and double-strand breaks (DSB) and, thus, inducing chromosomal aberrations (CA). MMC is a potent bifunctional mutagen acting as an alkylating agent, causing DNA cross-links and inducing sister chromatid exchanges (SCEs). The protective effect induced by low doses of tested chemicals was analysed in whole blood human lymphocytes using cytogenetic endpoints (CA for BLM and SCE for MMC, respectively) as a measure of chromosomal instability. There was a significant difference between the protective effects induced by BLM and MMC in the lymphocytes of the same group of donors. The pre-treatment with a low dose of BLM-induced almost 50% decrease in the frequency of CA induced by challenging dose (CD), while the protective effect of MMC was below 20%. The higher AR induced by BLM may be related to the repair processing of BLM-induced DNA-damages. There was also a variability in ARs among individuals, which may reflect the differences in individual DNA-repair capacity.