Analysis of 8-hydroxydeoxyguanosine among workers exposed to diesel particulate exhaust: comparison with urinary metabolites and PAH air monitoring

Oxidative DNA damage and repair, as measured by 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine and DNA samples were studied in association with work-related diesel exhaust exposure among garage and waste collection workers. Seasonal variations of the urinary 8-OHdG levels in pre- and two post-workshift urine samples of 29 exposed workers and 36 control persons were evaluated. The mean±SE levels of post-workshift 8-OHdG (μmol/mol crea) were 1.52±0.44 in winter and 1.61±0.33 in summer for the exposed workers, and 1.56±0.61 in winter and 1.43±0.49 in summer for the controls, respectively. No significant difference in the urinary 8-OHdG levels between exposed workers and control subjects in winter (p=0.923) and summer (p=0.350) was observed. A linear mixed model, adjusted for years of employment, age, ex/non-smoking and BMI, indicated no significant dose exposure-relationships between the urinary 8-OHdG and 15 PAH air concentrations nor between the 8-OHdG and 7 PAH monohydroxy-metabolites analyzed in the same workers. 8-OHdG was also analyzed in the mononuclear cell DNA of 19 exposed and 18 control subjects. The mean value of 8-OHdG/non-modified 2'-deoxyguanosine (8-OHdG/105 dG±SE) were 4.89±0.17 for the exposed and 4.11±0.16 for the control persons, which showed no correlation with the urinary 8-OHdG levels (r=0.01, n=28, P=0.96). The PAH exposure at workplaces was mainly composed of volatile compounds, particularly naphthalene, suggesting low exposure through the respiratory tract and a low effect of PAH in ROS induction.     

Gas chromatographic-mass spectrometric method for the determination of alkylresorcinols in human plasma

Alkylresorcinols can be found in high amounts in whole grain cereals, especially in rye. Previously it has not been possible to measure alkylresorcinols in plasma. In this paper a validated gas chromatographic-mass spectrometric method for the quantitative determination of alkylresorcinols with chain lengths of C15:0, C17:0, C19:0, C21:0, and C23:0 in human plasma samples is presented. Other alkylresorcinols may be measured with the method as well, but their assay was not validated in this work. In this work also the amount of alkylresorcinol C25:0 was measured. The pretreatment of plasma samples consists of a simple incubation, an extraction with diethyl ether and a chromatographic purification before the GC-MS analysis. As internal standard an alkylresorcinol C20:0 was used. The validation of the method showed that it fulfilled the reliability criteria. Calibration graphs were linear over the range of 4.1-660pg per injection. The mean recovery percentage was 112+/-10.8%. Our results show that the alkylresorcinols are found in plasma in the same ratio, as found in rye grains, according to literature. The alkylresorcinols were in the unconjugated form. The total amounts of alkylresorcinols in two plasma samples analyzed here were 333 and 381nmol/L.     

Studies on cystathionase activity in rat liver and brain during development. Effects of hormones and amino acids in vivo

High activity of cystathionase was present in rat liver but only low amounts of activity in rat brain during development. Triamcinolone had no effect on liver cystathionase activity in foetuses but increased the enzyme activity significantly in postnatal rats. l-Thyroxine decreased liver cystathionase activity significantly in newborn rats; administration of pyridoxal 5'-phosphate did not prevent this effect. l-Methionine significantly increased liver cystathionase activity in newborn rats.     

Effects of High Intensity Interval Training and Strength Training on Metabolic,Cardiovascular and Hormonal Outcomes in Women with Polycystic Ovary Syndrome: A Pilot Study

Background

Polycystic ovary syndrome is a common endocrinopathy in reproductive-age women, and associates with insulin resistance. Exercise is advocated in this disorder, but little knowledge exists on the optimal exercise regimes. We assessed the effects of high intensity interval training and strength training on metabolic, cardiovascular, and hormonal outcomes in women with polycystic ovary syndrome.

Materials and Methods

Three-arm parallel randomized controlled trial. Thirty-one women with polycystic ovary syndrome (age 27.2 ± 5.5 years; body mass index 26.7 ± 6.0 kg/m²) were randomly assigned to high intensity interval training, strength training, or a control group. The exercise groups exercised three times weekly for 10 weeks.

Results

The main outcome measure was change in homeostatic assessment of insulin resistance (HOMA-IR). HOMA-IR improved significantly only after high intensity interval training, by -0.83 (95% confidence interval [CI], -1.45, -0.20), equal to 17%, with between-group difference (p = 0.014). After high intensity interval training, high-density lipoprotein cholesterol increased by 0.2 (95% CI, 0.02, 0.5) mmol/L, with between group difference (p = 0.04). Endothelial function, measured as flow-mediated dilatation of the brachial artery, increased significantly after high intensity interval training, by 2.0 (95% CI, 0.1, 4.0) %, between-group difference (p = 0.08). Fat percentage decreased significantly after both exercise regimes, without changes in body weight. After strength training, anti-Müllarian hormone was significantly reduced, by -14.8 (95% CI, -21.2, -8.4) pmol/L, between-group difference (p = 0.04). There were no significant changes in high-sensitivity C-reactive protein, adiponectin or leptin in any group.

Conclusions

High intensity interval training for ten weeks improved insulin resistance, without weight loss, in women with polycystic ovary syndrome. Body composition improved significantly after both strength training and high intensity interval training. This pilot study indicates that exercise training can improve the cardiometabolic profile in polycystic ovary syndrome in the absence of weight loss.

Trial Registration

ClinicalTrial.gov NCT01919281     

Effects of High Intensity Interval Training on Pregnant Rats,and the Placenta,Heart and Liver of Their Fetuses

Objective

To investigate the effects of high intensity interval training (HIIT) on the maternal heart, fetuses and placentas of pregnant rats.

Methods

Female Sprague-Dawley rats were randomly assigned to HIIT or sedentary control groups. The HIIT group was trained for 6 weeks with 10 bouts of high intensity uphill running on a treadmill for four minutes (at 85–90% of maximal oxygen consumption) for five days/week. After three weeks of HIIT, rats were mated. After six weeks (gestational day 20 in pregnant rats), echocardiography was performed to evaluate maternal cardiac function. Real-time PCR was performed for the quantification of gene expression, and oxidative stress and total antioxidant capacity was assessed in the tissue samples.

Results

Maternal heart weight and systolic function were not affected by HIIT or pregnancy. In the maternal heart, expression of 11 of 22 genes related to cardiac remodeling was influenced by pregnancy but none by HIIT. Litter size, fetal weight and placental weight were not affected by HIIT. Total antioxidant capacity, malondialdehyde content, peroxidase and superoxide dismutase activity measured in the placenta, fetal heart and liver were not influenced by HIIT. HIIT reduced the expression of eNOS (p = 0.03), hypoxia-inducible factor 1α (p = 0.04) and glutathione peroxidase 4.2 (p = 0.02) in the fetal liver and increased the expression of vascular endothelial growth factor-β (p = 0.014), superoxide dismutase 1 (p = 0.001) and tissue inhibitor of metallopeptidase 3 (p = 0.049) in the fetal heart.

Conclusions

Maternal cardiac function and gene expression was not affected by HIIT. Although HIIT did not affect fetal growth, level of oxidative stress and total antioxidant capacity in the fetal tissues, some genes related to oxidative stress were altered in the fetal heart and liver indicating that protective mechanisms may be activated.     

Prenatal Metformin Exposure in Mice Programs the Metabolic Phenotype of the Offspring during a High Fat Diet at Adulthood

Aims

The antidiabetic drug metformin is currently used prior and during pregnancy for polycystic ovary syndrome, as well as during gestational diabetes mellitus. We investigated the effects of prenatal metformin exposure on the metabolic phenotype of the offspring during adulthood in mice.

Methods

Metformin (300 mg/kg) or vehicle was administered orally to dams on regular diet from the embryonic day E0.5 to E17.5. Gene expression profiles in liver and brain were analysed from 4-day old offspring by microarray. Body weight development and several metabolic parameters of offspring were monitored both during regular diet (RD-phase) and high fat diet (HFD-phase). At the end of the study, two doses of metformin or vehicle were given acutely to mice at the age of 20 weeks, and Insig-1 and GLUT4 mRNA expressions in liver and fat tissue were analysed using qRT-PCR.

Results

Metformin exposed fetuses were lighter at E18.5. There was no effect of metformin on the maternal body weight development or food intake. Metformin exposed offspring gained more body weight and mesenteric fat during the HFD-phase. The male offspring also had impaired glucose tolerance and elevated fasting glucose during the HFD-phase. Moreover, the expression of GLUT4 mRNA was down-regulated in epididymal fat in male offspring prenatally exposed to metformin. Based on the microarray and subsequent qRT-PCR analyses, the expression of Insig-1 was changed in the liver of neonatal mice exposed to metformin prenatally. Furthermore, metformin up-regulated the expression of Insig-1 later in development. Gene set enrichment analysis based on preliminary microarray data identified several differentially enriched pathways both in control and metformin exposed mice.

Conclusions

The present study shows that prenatal metformin exposure causes long-term programming effects on the metabolic phenotype during high fat diet in mice. This should be taken into consideration when using metformin as a therapeutic agent during pregnancy.     

Prevalence and antifungal drug sensitivity of non‐albicans Candida in oral rinse samples of self‐caring elderly

doi: 10.1111/j.1741‐2358.2010.00407.x
Prevalence and antifungal drug sensitivity of non‐albicans Candida in oral rinse samples of self‐caring elderly Aim: To assess the prevalence and antifungal drug sensitivity of non‐albicans Candida (NAC) species in elderly outpatients. Materials and methods: We investigated oral rinse samples of 194 self‐caring elderly population (mean age 83 years) with emphasis on background factors for harbouring NAC. Susceptibility of Candida species to antifungal drugs was determined using standard methodology. Multiple logistic regression analysis was performed taking positive NAC count as the dependent variable and a number of known Candida risk factors as independent variables. Results: Prevalence of candidal carriage of the population was 78.4%, of which 0.5% of the subjects were NAC positive. Candida dubliniensis was the most prevalent NAC species, followed by Candida glabrata and Candida parapsilosis. The NAC positive elderly were more often edentulous with dental prostheses or had fewer teeth than Candida albicans‐positive or yeast‐negative subjects. Dental caries slightly increased the risk for having NAC strains (odds ratio 1.08), whilst greater age appeared to lower the risk (odds ratio 0.77). Candida species were susceptible to the commonly used antifungal agents in general, but with considerable variation among species. Occasionally, some NAC exhibited lower antifungal susceptibility. Conclusion: The possibility of oral reservoirs of NAC strains which are resistant to common antifungals should be noted in elderly outpatients.     

Safety issues of Lactobacillus bulgaricus with respect to human gelatinases in vitro

In oral medicine and dentistry probiotics have shown promising results in controlling dental diseases and yeast infections. This study was made to investigate the effect of eight strains of Lactobacillus bulgaricus and their effects on human matrix metalloproteinase-9 (MMP-9). The hypothesis was that these bacteria used in yoghurt production for centuries are not proteolytic and thus can be safely used in the development of probiotic preparations. Bacterial cell fractions and supernatant specimens were prepared and studied with gelatinase zymography and MMP-9 activation was assessed by immunoblotting. The effect of synthetic MMP inhibitors and a serine protease inhibitor (Pefabloc) on bacterial proteinases was studied with zymography. The results showed very low gelatinolytic activity. There was a slight difference between the supernatant and cell fractions so that the supernatant specimens produced weak gelatinolytic bands in zymography while hardly anything was seen in the cell fraction series. The tested synthetic MMP inhibitors and Pefabloc did not affect the proteolytic activity of the lactobacilli strains. The lactobacilli did not seem to induce the conversion of proMMP-9 to its active form. Consequently, our study hypothesis was confirmed and the studied Lactobacillus strains are not likely to degrade host tissue components.