Interleukin 25, thymic stromal lymphopoietin and house dust mites in pathogenesis of atopic dermatitis.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in the world. It is characterized by recurrent eczematous skin lesions, fluctuating course and chronic pruritus. Increasing evidence suggest that AD is more common in adults than previously thought. The disease is characterized by an impaired skin barrier, aberrant Th2-type cytokine production and intensive pruritus. Epithelial keratinocytes constitute the first physical, chemical and immunological barrier, classified as a part of the innate defense system. These keratinocytes secrete various factors, e.g. alarmins such as thymic stromal lymphopoietin (TSLP) and interleukin 25 (IL-25). Serum levels of substance P (SP) have been reported to be increased in patients with AD and correlated with itch intensity. Several previous studies reported a positive association between AD severity and house dust mites (HDM) sensitization. The aim of the study was to analyze IL-25, TSLP and SP concentrations in blood serum of adult patients with severe AD, depending on the degree of allergy to HDM. There were 31 adult AD patients enrolled into the study and a control group that consisted of 20 healthy subjects. AD was diagnosed on the basis of Hanifin and Rajka criteria. SCORing Atopic Dermatitis (SCORAD) and visual analogue (VAS) scores were used to assess the intensity of pruritus and blood content of specific IgE to HDM, as well as TSLP, IL-25 cytokines and SP was measured. Our study presents the evidence that IL-25 serum concentration is increased in patients with atopic dermatitis and this cytokine plays an important role in pathogenesis of this disease. HDM could stimulate the release of IL-25 which aggravates the disease severity. Our results corroborate previous findings on the role of TSLP in atopic dermatitis.

Coffee consumption and risk of hypertension in the Polish arm of the HAPIEE cohort study.

BACKGROUND/OBJECTIVES: Coffee consumption has been hypothesized to be associated with blood pressure (BP), but previous findings are not homogeneous. The aim of this study was to evaluate the association between coffee consumption and the risk of developing hypertension. SUBJECTS/METHODS: Data on coffee consumption, BP and use of anti-hypertensive medicament were derived from 2725 participants of the Polish arm of the HAPIEE project (Health, Alcohol and Psychosocial factors In Eastern Europe) who were free of hypertension at baseline and followed up for an average of 5 years. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by multivariate logistic regression analyses and stratified for potential confounding factors. RESULTS: Coffee consumption was related to decreased age, smoking status and total energy intake. Compared with persons who drink <1 cup coffee per day, systolic BP was significantly associated with coffee consumption and the risk of hypertension was lower for individuals consuming 3-4 cups per day. Despite the analysis stratified by gender showed that the protective effect of coffee consumption on hypertension was significant only in women, the analysis after stratification by smoking status revealed a decreased risk of hypertension in non-smokers drinking 3-4 cups of coffee per day in both sexes (OR 0.41, 95% CI: 0.21, 0.79 for men and OR 0.54, 95% CI: 0.29, 0.99 for women). Upper category coffee consumption (>4 cups per day) was not related to significant increased risk of hypertension. CONCLUSIONS: Relation between coffee consumption and incidence of hypertension was related to smoking status. Consumption of 3-4 cups of coffee per day decreased the risk of hypertension in non-smoking men and women only.

Age at natural menopause in three central and eastern European urban populations: the HAPIEE study.

OBJECTIVES: To investigate the age at menopause in three urban populations in Central and Eastern Europe and to assess whether the (suspected) differences can be explained by a range of socioeconomic, reproductive and behavioural factors. METHODS: The Health, Alcohol and Psychosocial factors in Eastern Europe (HAPIEE) Study examined random samples of populations aged 45-69 years in Novosibirsk (Russia), Krakow (Poland) and six Czech towns. Participants completed a questionnaire and attended an examination in clinic. A total of 12,676 of women were included in these analyses. RESULTS: The median age at menopause was 50 years in Novosibirsk, 51 years in Czech towns and 52 years in Krakow; the Cox regression hazard ratios of menopause, compared with Krakow, were 1.47 (95% CI 1.40-1.55) for Novosibirsk and 1.10 (1.04-1.16) for Czech women. In multivariate analyses, higher education, using vitamin and mineral supplements and ever use of oral contraceptives were associated with later menopause, while smoking, abstaining from alcohol and low physical activity were associated with earlier menopause. These factors, however, did not explain the differences between populations; the multivariate hazard ratios of menopause, compared with Krakow, were 1.48 (1.40-1.57) for Novosibirsk and 1.11 (1.05-1.17) for Czech women. CONCLUSIONS: In this large population based study, differences in age at menopause between Central and Eastern Europe populations were substantial and unexplained by a range of risk factors. Associations of age at menopause with risk factors were largely consistent with studies in other populations.

Direct estimate of the mutation rate and the distribution of fitness effects in the yeast Saccharomyces cerevisiae.

Estimates of the rate and frequency distribution of deleterious effects were obtained for the first time by direct scoring and characterization of individual mutations. This was achieved by applying tetrad analysis to a large number of yeast clones. The genomic rate of spontaneous mutation deleterious to a basic fitness-related trait, that of growth rate, was U = 1.1 x 10(-3) per diploid cell division. Extrapolated to the fruit fly and humans, the per generation rate would be 0.074 and 0.92, respectively. This is likely to be an underestimate because single mutations with selection coefficients s < 0.01 could not be detected. The distribution of s > or = 0.01 was studied both for spontaneous and induced mutations. The latter were induced by ethyl methanesulfonate (EMS) or resulted from defective mismatch repair. Lethal changes accounted for approximately 30-40% of the scored mutations. The mean s of nonlethal mutations was fairly high, but most frequently its value was between 0.01 and 0.05. Although the rate and distribution of very small effects could not be determined, the joint share of such mutations in decreasing average fitness was probably no larger than approximately 1%.

Environmental stress and mutational load in diploid strains of the yeast Saccharomyces cerevisiae.

The negative effect of permanent contamination of populations because of spontaneous mutations does not appear to be very high if judged from the relatively good health of humans or many wild and domesticated species. This is partly explained by the fact that, in diploids, the new mutations are usually located in heterozygous loci and therefore are masked by wild-type alleles. The expression of mutations at the phenotypic level may also strongly depend on environmental factors if, for example, deleterious alleles are more easily compensated under favorable conditions. The present experiment uses diploid strains of yeast in which mutations arise at high rates because a mismatch-repair protein is missing. This mutagenesis resulted in a number of new alleles that were in heterozygous loci. They had no detectable effect on fitness when the environment was benign. A very different outcome was seen when thermal shock was applied, where fitness of the mutation-contaminated clones was lower and more diverse than that of the nonmutagenized clones. This shows that the genetic load conferred by spontaneous mutations can be underestimated or even overlooked in favorable conditions. Therefore, genetic variation can be higher and natural selection more intense when environmental conditions are getting poorer. These conclusions apply, at least, to that component of variation that directly originates from spontaneous mutations (as opposed to the variation resulting from the history of selection).

[Prevalence of type II diabetes mellitus in population of Krakow]. / Chorobowosc z powodu cukrzycy typu 2 w populacji Krakowa.

UNLABELLED: The study was carried out within a framework of the Polish Multicenter Study on Diabetes Epidemiology in 1998-2000. The aim of the study was to define the prevalence of type 2 diabetes, especially unknown diabetes, and prevalence of impaired glucose tolerance in a demographically well-defined urban population using the comparable epidemiological methods which were applied in the previous study in Wroclaw in 1985-1986. The study was carried out in 200,000 subjects inhabiting the town quarter. Out of those who were 35 or more 6000 subjects were randomised using a table of random numbers. All randomized subjects received a letter of invitation explaining the sense of study, its objectives and methods. If necessary the invitations were renewed, and then the subjects were contacted by phone. Each responding person received a questionnaire to complete. Then anthropometric and blood pressure measurements were taken. Blood was sampled for plasma glucose, insulin, total cholesterol, HDL cholesterol and triglycerides in the fasting state. Those who declared being non-diabetic and in whom screening test using a glucometer (Glucotrend) revealed fasting glycemia below 8 mmol/l underwent an oral glucose tolerance test (75 g) to determine glycemia and insulinemia at 120 min. Plasma glucose, total cholesterol, HDL cholesterol and triglycerides concentrations were measured with an enzymatic method, whereas insulinemia was defined with the IRMA technique, using ready kits Swierk-Poland. Diabetes mellitus and impaired glucose tolerance were recognised according to the 1985 WHO criteria. Chi square test, Fisher's test and Mann-Whitney test were used for statistical analysis. Statistical analysis was carried out using the statistical package BMDP. During 3 years of the study out of 6000 randomly selected subjects 3060 (1731 women and 1329 men) responded. In the study population 192 patients were with known diabetes, including 150 subjects receiving oral antidiabetic agents or insulin at the time of the study or some with high fasting glycemia not receiving any treatment except a diet. The 42 subjects who prior to the study had not been receiving hypoglycemic agents or in whom fasting glycemia had been below 8 mmol/l underwent an oral glucose tolerance test. Of them diabetes was confirmed in 11 patients, impaired glucose tolerance was observed in 9, and glucose intolerance was excluded in 22 subjects. Thus, in the study group 161 subjects (75 women and 86 men) with a mean age 61.5 +/- 8.95 years had already diabetes. Their mean BMI was 31.5 +/- 4.6 kg/m2 and did not differ significantly between both sexes. Only HDL cholesterol was significantly higher in men (women 1.1 +/- 0.3 vs. men 1.3 +/- 0.3, p < 0.001) in this group. Among those who declared being non-diabetic 160 subjects (77 men and 83 women), mean age 58.0 +/- 9.7 years and mean BMI 31.4 +/- 4.9 kg/m2 had diabetes identified according to the 1985 WHO criteria. Fasting insulinemia was 16.6 +/- 12.0 uj/ml in this group. At 120 min OGTT insulinemia in women was higher than in men (152.6 +/- 90.5 vs. 112.0 +/- 83.4, p < 0.01). In the whole study population diabetes was found in 321 subjects, including 161 with known and 160 with newly diagnosed diabetes. Based upon these data a standardized prevalence rate due to type 2 diabetes was calculated being 5.37% for the whole population (2.82% for known and 2.55% for unknown diabetes, respectively). When only part of the population over 35 years of age was taken into consideration, the rate was 10.77% (5.66% for known and 5.11% for unknown diabetes). When only fasting glycemia according to ADA recommendation was analysed, diabetes was recognised in 160 subjects (107 men and 53 women). In 78 subjects (49 men and 29 women) diabetes was diagnosed according to the WHO and ADA criteria. When oral glucose tolerance test and glycemia at 120 min exceeding 11.1 mmo/l is considered a gold standard for the diagnosis of diabetes, the diagnostic accuracy of the ADA criteria is 48.7%. In the study population 449 (14.55%) subjects (201 men and 248 women), mean age 56.6 +/- 9.6 years and mean BMI 29.7 +/- 4.6 (men 29.0 +/- 3.7 vs. women 30.2 +/- 5.2, p < 0.01) had impaired glucose tolerance. In our study population there were 572 subjects (329 men and 243 women) with impaired fasting glucose. Of them 359 subjects (212 men and 147 women) had normal glucose tolerance in OGTT, 161 (99 men and 62 women) had impaired glucose tolerance, and 52 (18 men and 62 women) type 2 diabetes. Thus, of the 572 subjects 9% (5.4% of men and 13% of women) had diabetes type 2, and 28% (30% of men and 25% of women) had impaired glucose tolerance. As the frequency of impaired glucose tolerance in this subgroup is higher than in the whole study population it seems justified to identify a group of subjects with increased fasting glycemia and to administer OGTT. CONCLUSIONS: 1. A significant rise in the prevalence of type 2 diabetes was observed between 1986 and 2000 (from 3.7% to 10.77%). 2. Prevalence of unknown diabetes increased considerably (reaching 5.11%). 3. The similar rise in the prevalence of impaired glucose tolerance was observed between 1986 and 2000 (from 2.9% to 14.5%) 4. Early detection of type 2 diabetes should be based upon oral glucose tolerance test according to the WHO.

Spatial variability and trends in ambient air concentrations of metals in Cracow, Poland.

Even though the air quality has been improving since the beginning of the 1980s, Cracow still belongs to the most polluted cities in Poland. The air pollution originates mainly from industry, small-size emission sources and transport. Metals in ambient air have been monitored since 1992 by 4 stations located within the city. The aim of the study was to determine the city areas where the national limits of heavy metals in suspended particles are exceeded and to assess the trends for the years 1992-1999. The monthly mean and maximum values of lead, zinc, chromium, copper, cadmium, nickel and iron were used in the analysis. Between 1992 and 1999, the level of most monitored metals in suspended particles was much below the national standards. Only the concentration of lead exceeded the limits by 50% in the area with the station monitoring traffic air pollution. However, the substantial variability in concentrations of monitored metals observed within the city was most pronounced around the metallurgical plant. Nowadays a new factor prevails: heavy traffic has resulted in a substantially enhanced concentration of lead across the city.

[The effect of short-term changes in levels of air pollution on mortality from cardiovascular diseases among inhabitants of Krakow]. / Wplyw krótkotrwalych zmian poziomu zanieczyszczen powietrza atmosferycznego na umieralnosc z powodu chorób ukladu krazenia wsród mieszkanców Krakowa.

The analysis of short term relation between daily ambient air pollution and daily number of deaths in Kraków, Poland, during the period 1993-1996 was the purpose of the study. The exposure time series data dealt with sulphur dioxide (SO2) and particles with aero-diameter smaller than 10 microns (PM10). Daily mortality due to all causes and cardiovascular diseases were considered separately for two age groups. The statistical procedures included modelling of potential confounding factors (seasonal patterns, meteorological factors) and in the final analysis the Poisson regression model was applied. Effects were expressed as relative risks per 100 micrograms/m3 increase of the corresponding pollutant levels. It was found that sulphur dioxide was significantly related to mortality from all causes and cardiovascular conditions in the age group 65 years and over whereas the effect of suspended particles was at the borderline significance level. The relative risk of cardiovascular death associated with 100 micrograms/m3 increment of mean daily SO2 was 1.17 (1.10-1.25) in the total sample under study, higher for men (RR = 1.27, CI: 1.12-1.45) than for women (RR = 1.12, CI: 1.01-1.23). The corresponding RRs for PM10 and cardiovascular deaths were 1.06 (0.98-1.16) for men and 1.07 (0.99-1.13) for women. These results strengthen the evidence of casual relationship between ambient air pollution level and daily mortality and pinpoints important health hazards issues for the Kraków inhabitants.

A clinico-epidemiological study on gastritis in gastric carcinoma and in non-cancerous gastric pathology in Poland.

To investigate the risk of gastric cancer development in subjects with atrophic and nonatrophic gastritis, we studied 221 consecutive gastric cancer patients and 7647 non-cancer subjects for whom endoscopic biopsy of the gastric mucosa was available. In gastritis patients, the relative risk (RR) estimates of gastric cancer were as follows: corpus atrophic gastritis RR = 8.7 (95% CI = 5.4-14.1), antral atrophic gastritis RR = 4.5 (2.4-8.1), chronic atrophic pangastritis RR = 7.6 (3.8-15.3), corpus nonatrophic gastritis RR = 1.6 (0.9-2.7), antral non-atrophic gastritis RR = 1.2 (0.7-2.3), and pangastritis RR = 1.3 (0.6-2.8). The latter was of borderline significance (p = 0.07). In peptic ulcer, a significant excess risk was calculated for subjects with either corpus atrophic gastritis (RR = 3.1 [2.5-3.9] or antral atrophic gastritis (RR = 3.5 [2.6-4.8]). For stomach polyps, the risk was significantly increased only in subjects with corpus atrophic gastritis (RR = 2.1 [1.3-3.5]). The risks for both peptic ulcer and polyps, however, were significantly increased in chronic atrophic pangastritis. A substantial excess risk of gastric cancer was found for atrophy in the corpus (RR = 20.9 [9.0-48.9]) and in the antrum (RR = 14.9 [5.3-41.9]). An increased risk of peptic ulcer was also confirmed in subjects with atrophy in the corpus (RR = 3.0 [1.3-6.9]) and in the antrum (RR = 4.9 [2.0-12.1]).