DNA damage from polycyclic aromatic hydrocarbons measured by benzo[a]pyrene-DNA adducts in mothers and newborns from Northern Manhattan, the World Trade Center Area, Poland, and China.

Polycyclic aromatic hydrocarbons (PAH), of which benzo[a]pyrene is a representative member, are combustion-related environmental pollutants and include known carcinogens. Laboratory animal studies indicate that the dose of PAHs to the fetus is on the order of a 10th that to the mother and that there is heightened susceptibility to PAH-induced carcinogenesis during the fetal and infancy periods. Carcinogen-DNA adducts, a measure of procarcinogenic genetic damage, are considered a biomarker of increased cancer risk. Here we compare the levels of benzo[a]pyrene-DNA adducts as a proxy for PAH-DNA damage measured in maternal blood and newborn cord blood obtained at delivery in four different populations of mothers (total of 867) and newborns (total of 822), representing a 30-fold range of exposure to ambient PAHs. The populations include residents in Northern Manhattan, participants in a study of the effects of the World Trade Center disaster, residents in Krakow, Poland, and residents in Tongliang, China. Mean adduct concentrations in both maternal and cord blood and the proportion of samples with detectable adducts, increased across the populations [Northern Manhattan < World Trade Center (WTC) < Krakow < Tongliang], consistent with the trend in estimated ambient exposure to PAHs (P < 0.001). For mothers, the means in the respective populations were Northern Manhattan (0.21 adducts per 10(8) nucleotides), WTC (0.23 adducts per 10(8) nucleotides), Krakow (0.28 adducts per 10(8) nucleotides), Tongliang (0.31 adducts per 10(8) nucleotides); the corresponding means in the newborns were Northern Manhattan (0.23), WTC (0.24), Krakow (0.29), Tongliang (0.31). The percentage of mothers with detectable levels of adducts in the respective populations were Northern Manhattan (36.8%), WTC (57.5%), Krakow (72.9%), Tongliang (73.4%); the corresponding percentages among the newborns were Northern Manhattan (42.4%), WTC (60.6%), Krakow (71.1%), Tongliang (79.5%). Despite the estimated 10-fold lower PAH dose to the fetus based on laboratory animal experiments, the adduct levels in the newborns were similar to or higher than in the mothers. This study suggests that the fetus may be 10-fold more susceptible to DNA damage than the mother and that in utero exposure to polycyclic aromatic hydrocarbons may disproportionately increase carcinogenic risk. The data support preventive policies to limit PAH exposure to pregnant women and children.     

Are chronic wheezing and asthma-like attacks related to FEV1 decline? The Cracow study

Analysis is presented of the relationship between decline in ventilatory function and possible symptoms of bronchial hypereactivity. Data comes from three consecutive surveys within a 13-year follow-up study of a population sample of 1747 persons (718 males and 1029 females) who completed spirometric testing and interviews. Chest symptoms recorded in the two initial surveys were used as baselines for the prognostic study on FEV₁ change. To evaluate changes in lung function the FEV₁ decline index, expressed as percentage of FEV₁ loss during the study period, was calculated. Chronic wheezing and asthma-like attacks were very strongly related to FEV₁ baseline level. Multiple linear regression analysis for each separate symptom including age and smoking habits as confounders and showed that the FEV₁ decline index was higher and more significant when wheezing and asthma-like attacks or chronic cough were present. When the combination of symptoms were introduced into the regression model, the effect of wheezing became insignificant. Only attacks of shortness of breath in both sexes and chronic cough in women were significantly associated with more rapid FEV₁ decline. However, the effect of persistent wheezing in men had a rather substantial impact on FEV₁ change. Comparing the effect of the number of cigarettes smoked with the effect of symptoms, one can see that FEV₁ decline due to attacks of shortness of breath is comparable to that seen with heavy smoking. There was no strong evidence that the symptoms under study precede the more rapid FEV₁ decline.     

Pharmacokinetic and pharmacodynamic effects of the novel benzodiazepine antagonist 2-phenylpyrazolo[4,3-c]quinolin-3(5H)-one in humans

2-Phenylpyrazolo[4,3-c]quinolin-3(5H)-one (CGS 8216) is pharmacologically characterized as benzodiazepine antagonist with low inverse agonistic effects. Single oral doses up to 650 mg and subchronic doses up to 100 mg daily for seven days are well tolerated by young healthy volunteers. Plasma concentrations of CGS 8216 are variable, not dose-related and relatively low considering the doses administered. A high plasma concentration ratio of metabolite vs. parent compound (3:1) points to an extensive gastrointestinal first-pass metabolism. CGS 8216 influences the human electroencephalogram similar to anxiolytic and vigilance enhancing drugs in doses which do not change performance of psychometric tests. CGS 8216 antagonizes the diazepam-induced impairment of alertness.     

Nitric oxide mediates intestinal hyperaemic responses to intraluminal bile-oleate

It has long been recognized that intestinal blood flow increases at mealtimes. Mesenteric hyperaemia is also evoked by activation of sensory peptidergic nerves. Our studies explored the possible role of endogenous nitric oxide (NO) in the rat intestinal vasodilator response to luminal instillation of an oleic acid plus bile mixture before and after acute intrajejunal instillation of capsaicin and after chronic pretreatment with capsaicin. In anaesthetized rats we measured jejunal blood flow (BF) with an ultrasonic Doppler flowmeter and systemic arterial pressure (AP) with a pressure transducer. Intestinal perfusion with 80 mM oleic acid in bile increased BF by 98±12%. Instillation of 4 mg of capsaicin into the jejunal lumen initially increased BF by 42±9% but was followed by vasoconstriction. Inhibition of NO synthase with 25 mg/kg i.v. N-nitro-L-arginine (L-NNA) decreased BF by 27±5% and increased AP by 37±11%. After treatment with L-NNA and after acute and chronic administration of capsaicin, the bile-oleate-induced maximal increases in BF above control levels were 42±7%, 65±12%, and 58±8%, respectively. The observed inhibitory effect of L-NNA on the intestinal hyperaemic response to the bile-oleate mixture was reversed by pretreatment with L-arginine (100 mg/kg i.V.). In capsaicin pretreated rats the subsequent bile-oleate-induced hyperaemia was reduced in magnitude but the inhibitory effects of L-NNA were proportionately the same as in animals not receiving capsaicin. These findings support the hypothesis that NO is involved with bile-oleate-induced mesenteric hyperaemia.     

Influence of exposure mode on vinyl chloride action

Rats were subjected to 4 h continuous or intermittent exposure to vinyl chloride (VC) at different time-weighted average concentrations (15, 50, 150, 500 and 15,000 mg/m³). Hepatic non-protein sulfhydryl content (NPSH) and excretion of thiodiglycolic acid (TdGA) in urine were determined. VC at concentrations from 50 mg/m³ to 15,000 mg/m³ caused a dose-dependent depression of NPSH, but no difference in the magnitude of this depression induced by continuous or intermittent exposure at the same average concentration of VC was noted. At average concentrations of 50 mg/m³ and 150 mg/m³, the urinary excretion of TdGA under continuous exposure did not differ from that under intermittent exposure, whereas at VC concentrations of 500 mg/m³ and 15,000 mg/m³ it was higher following continuous exposure.     

Functional status of the lower extremities in elderly males. A community study

The purpose of this study was to evaluate the functional status of the lower extremities (FSL) of elderly males from the community and to compare it with the self-assessment of health status (SHS) and ventilatory lung function based on measurement of forced expiratory vital capacity (FVC). The material covered a group of 559 males, age 65-89 years, who are residents of Krakow. The FSL was measured by the length of standing time on one leg (ST). There was a very strong declining trend in the ST with age in the elderly. The ST correlated significantly inversely with age (r=-0.32) and positively with FVC (r=0.29). The FSL was also associated strongly with the SHS score, while body-mass index (BMI) and occupational category (OC) appeared to have insignificant effect. The results of the study suggest that the ST may be used as a crude indicator of the general fitness of the elderly.     

The adverse effect of low levels of ambient air pollutants on lung function growth in preadolescent children.

The main purpose of our study was to assess the effect of low concentrations of ambient air pollution on lung function growth in preadolescent children. We accounted for height velocity over the follow-up period and also for other possible confounders such as baseline anthropometric and physiologic characteristics of children. In addition to outdoor air pollution, we considered the possible effects of social class and exposure to indoor pollutants such as gas stove fumes or environmental tobacco smoke. The cohort prospective study was carried out in 1,001 preadolescent children from two areas of Krakow, Poland, that differed in ambient air pollutants. In the city center (higher pollution area), the mean annual level [+/- standard deviation (SD)] of suspended particulate matter was 52.6 +/- 53.98 microg/m(3) and that of SO(2) was 43.87 +/- 32.69 microg/m(3); the corresponding values in the control area were 33.23 +/- 35.99 microg/m(3) and 31.77 +/- 21.93 microg/m(3). Mean lung function growth rate adjusted to height velocity and lung function level at the study entry was significantly lower in boys and girls living in the more polluted areas. Also, the proportion of children with the slower lung function growth (SLFG) was higher in the children from the more polluted area of the city. The analysis completed in the group of children after the exclusion of asthmatic subjects and those with asthmalike symptoms confirmed that, in boys, odds ratios (ORs) for SLFG [forced vital capacity (FVC)] and air pollution after adjustment to baseline FVC, height, and growth rate was significant [OR = 2.15; 95% confidence interval (CI), 1.25-3. 69)]. The analysis also confirmed that for SLFG(FEV(1)) the OR was 1. 90 (CI, 1.12-3.25). The corresponding OR values in girls were insignificant (OR = 1.50; CI, 0.84-2.68 and OR = 1.39; CI, 0.78-2. 44). The association between ambient pollutants and poorer gain of pulmonary volumes in children living in more polluted areas suggests that air pollution in the residence area may be a part of the causal chain of reactions leading to retardation in pulmonary function growth during the preadolescent years.     

Case-control study of lifetime occupational and recreational physical activity and risks of colon and rectal cancer.

Important aspects of the inverse relation between physical activity and colon cancer risk are still under discussion. In 2000-2003, 239 incident cases of colorectal cancer confirmed by histopathology and 239 hospital-based controls, matched by age and gender, were enrolled. In standardized interviews, data on occupational and recreational physical activity for ages 20, 30, 40, 50 and 60 years were collected from 98 colon cancer cases, 141 rectal cancer cases, and from 193 controls. Besides lifestyle and sociodemographic characteristics, a detailed food frequency questionnaire was assessed. In multivariate logistic regression for colon cancer, significant risk reductions for the highest quartile of total physical activity were found for almost all ages. For lifetime mean physical activity, the multivariate odds ratio for the highest quartile was 0.37 [95% confidence interval (CI) 0.17, 0.83]. For lifelong constantly high-exercisers compared with lifelong non-exercisers an odds ratio of 0.26 (95% CI 0.08, 0.84) was estimated. For rectal cancer, no consistent association with physical activity was found. No confounding effects were observed but the authors found effect modification with total energy intake. These data support an inverse association of colon cancer risk and physical activity which is most expressed if activity is kept up throughout life.     

Psychological aspects of erectile and ejaculatory dysfunction

Psychological factors play the most important role in the genesis of sexual dysfunction and the role of psychologists in the prevention, diagnosis, and treatment of these dysfunctions is therefore considerable. This article discusses some of the psychological factors that accompnay erectile ejaculatory cysfunction as well as the possible psychological mechanisms that can occur during the development of these dysfunctions.     

Immunohistologic studies of differential HLA expression in patients with various intestinal diseases

Histocompatibility antigens (HLA) play an important part in immunoregulation and in cell differentiation. This study analyses the expression of HLA class I and class II antigens (DR, DP, DQ) in intestinal biopsy specimen from patients with Crohn's disease, ulcerative colitis, GvHD, radiation colitis and intestinal adenomas using the indirect immunoperoxidase technique. 92 of 94 inflamed specimen from patients with inflammatory bowel disease showed a neoexpression of HLA II (DR greater than DP greater than DQ) on their epithelial cells. The intensity of HLA-DR neoexpression was significantly dependent on an endoscopic as well as a histological index of inflammation. All 75 non-inflamed specimen except 4 from patients with Crohn's disease did not show any evidence of HLA II display on the epithelium. 4 of 18 intestinal adenomas expressed HLA II on their epithelial cells without any correlation to the type of adenoma or the degree of cell dysplasia. Furthermore all specimen from a patient with intestinal GvHD showed an aberrant epithelial HLA II expression, but not that from radiation colitis. The expression of HLA class I antigens was similar in all biopsies studied. Our results suggest, that the epithelial neoexpression of HLA class II antigens may be an important event in the pathogenesis of various bowel diseases.