Particulate air pollution is associated with cardiovascular morbidity. One hypothesized mechanism involves oxidative stress, systemic inflammation, and endothelial dysfunction.
To assess an intervention's impact on particle exposures and endothelial function among healthy adults in a woodsmoke-impacted community. We also investigated the underlying role of oxidative stress and inflammation in relation to exposure reductions.
Portable air filters were used in a randomized crossover intervention study of 45 healthy adults exposed to consecutive 7-day periods of filtered and nonfiltered air.
Reactive hyperemia index was measured as an indicator of endothelial function via peripheral artery tonometry, and markers of inflammation (C-reactive protein, interleukin-6, and band cells) and lipid peroxidation (malondialdehyde and 8-iso-prostaglandin F(2a)) were quantified. Air filters reduced indoor fine particle concentrations by 60%. Filtration was associated with a 9.4% (95% confidence interval, 0.9-18%) increase in reactive hyperemia index and a 32.6% (4.4-60.9%) decrease in C-reactive protein. Decreases in particulate matter and the woodsmoke tracer levoglucosan were associated with reduced band cell counts. There was limited evidence of more pronounced effects on endothelial function and level of systemic inflammation among males, overweight participants, younger participants, and residents of wood-burning homes. No associations were noted for oxidative stress markers.
Air filtration was associated with improved endothelial function and decreased concentrations of inflammatory biomarkers but not markers of oxidative stress. Our results support the hypothesis that systemic inflammation and impaired endothelial function, both predictors of cardiovascular morbidity, can be favorably influenced by reducing indoor particle concentrations.
In postmenopausal women, we investigated if the response in bone mineral density (BMD) was associated with the response in the atherogenic lipid profile during hormone replacement therapy.
We performed an exploratory, post-hoc analysis of data from a prospective double-blind placebo-controlled trial. Healthy postmenopausal women were randomised into five groups, each receiving different combinations of 17 beta-estradiol and gestodene or placebo. A total of 133 women completed the study. The study period was 3 years. The response in bone mass was expressed as the percentage change in BMD from baseline calculated by linear regression from semi-annual measurements. The change in lipid profile was evaluated as the average of three mid-cycle and end-cycle values in percentage from baseline in order to account for cyclic changes during sequential hormone therapy.
A significant correlation between the increase in BMD of the spine and hip and forearm with the decrease in serum low density lipoprotein (LDL) and cholesterol was found. Additionally, the decrease in atherogenic lipids correlated significantly with the response in biochemical bone markers for resorption and formation.
In conclusion, our study shows that it is the same women who have a favourable response in BMD as in the lipid-profile during hormone replacement therapy (HRT). The association is most likely driven by a common response in FSH to exogenous estradiol therapy. This indicates that common denominators for the response to HRT exist. Further studies are needed to explore and identify such predictors.
Human exposure to genotoxic compounds present in ambient air has been studied using selected biomarkers in nonsmoking Danish bus drivers and postal workers. A large interindividual variation in biomarker levels was observed. Significantly higher levels of bulky carcinogen-DNA adducts (75.42 adducts/10(8) nucleotides) and of 2-amino-apidic semialdehyde (AAS) in plasma proteins (56.7 pmol/mg protein) were observed in bus drivers working in the central part of Copenhagen, Denmark. In contrast, significantly higher levels of AAS in hemoglobin (55.8 pmol/mg protein), malondialdehyde in plasma (0. 96 nmol/ml plasma), and polycyclic aromatic hydrocarbon (PAH)-albumin adduct (3.38 fmol/ microg albumin) were observed in the suburban group. The biomarker levels in postal workers were similar to the levels in suburban bus drivers. In the combined group of bus drivers and postal workers, negative correlations were observed between bulky carcinogen-DNA adduct and PAH-albumin levels (p = 0.005), and between DNA adduct and [gamma]-glutamyl semialdehyde (GGS) in hemoglobin (p = 0.11). Highly significant correlations were found between PAH-albumin adducts and AAS in plasma (p = 0.001) and GGS in hemoglobin (p = 0.001). Significant correlations were also observed between urinary 8-oxo-7, 8-dihydro-2'-deoxyguanosine and AAS in plasma (p = 0.001) and PAH-albumin adducts (p = 0.002). The influence of the glutatione S-transferase (GST) M1 deletion on the correlation between the biomarkers was studied in the combined group. A significant negative correlation was only observed between bulky carcinogen-DNA adducts and PAH-albumin adducts (p = 0.02) and between DNA adduct and urinary mutagenic activity (p = 0.02) in the GSTM1 null group, but not in the workers who were homozygotes or heterozygotes for GSTM1. Our results indicate that some of the selected biomarkers can be used to distinguish between high and low exposure to environmental genotoxins.
Exposure to diisocyanates is a known occupational hazard. One method for monitoring occupational exposure is by analyzing biomarkers in hydrolyzed urine and plasma. The half-life of the biomarkers in plasma is about 3 weeks, and the urinary elimination is divided into one fast (hours) and one slow phases (weeks). Polymorphism in glutathione S-transferase enzymes (GST) is earlier shown to modify the metabolism. The aim of the study was to assess whether biomarkers of exposure in urine collected after two non-exposed days correlate with levels in plasma and whether they can be used as a measure for long-term exposure to aromatic diisocyanates and further whether polymorphisms in GST influenced the correlations.
Biomarkers of exposure was analyzed in urine and blood samples collected from 24 workers, exposed to at least one of toluene-, methylenediphenyl- or naphthalene diisocyanate, on a Monday morning after at least two unexposed days. Moreover, genotype was determined for 19 of the workers.
The corresponding specific gravity-adjusted biomarkers in urine and plasma levels for the different diisocyanates correlated well (r between 0.689 and 0.988). When taking all samples together, the correlation coefficient was 0.926. Polymorphism in the GSTM1 genotype seemed to modify the association.
Urine collected after two unexposed days can possibly be used as long-term biomarker of exposure for aromatic diisocyanates.
Low blood serum/plasma concentrations of ochratoxin A (OTA) have been reported for healthy persons in more than 20 countries. Epidemiology studies in Bulgaria, Romania, Spain, the Czech Republic, Turkey, Italy, Egypt, Algeria and Tunisia have found significantly higher serum or plasma levels of OTA in patients with certain kidney disorders compared to healthy people, although the association may not be a causal one. Regional variations within one country, seasonal differences and variation within one person were found in some studies. Correlations with age and gender have not usually been detected. Detection limits using liquid chromatographic methods are about 0.02-0.1 ng ml(-1) plasma/serum so that incidences of positives often are 50-100%, reflecting widespread and continuous exposure of humans to OTA. In a study in the UK, OTA in urine was found to be a better indicator of OTA consumption than OTA in plasma. Nevertheless, blood plasma concentrations have been widely used to estimate dietary intake of OTA, using equations relating it with plasma concentration, plasma clearance and bioavailability. A further source of human exposure is airborne dust. OTA has been detected in human milk in several countries and comparisons with serum/blood levels have been made in Germany and Sweden.
Still little is known about the manifestations of osteogenesis imperfecta (OI) in adults. We therefore initiated this study of bone mass, bone turnover and prevalence of fractures in a large cohort of adult patients. We found a surprising low prevalence (10%) of osteoporosis. These patients, however, expressed the most severe disease.
To characterize bone mineral density, bone turnover, calcium metabolism and prevalence of fractures in a large cohort of adults with osteogenesis imperfecta.
One hundred fifty-four patients with adult OI participated and 90 (age range 25-83) provided dual X-ray absorptiometry (DXA) measurements. According to Sillence classification criteria, 68 persons were classified as OI type I, 9 as type III, 11 type IV and 2 were unclassified. Fracture numbers were based on self-reporting. Biochemical markers of bone turnover were measured and bone mineral density (BMD) of the spine, femoral neck and total body were determined by DXA.
Only 10% of adults with OI exhibited osteoporotic T scores (T?=?-2.5) but compared to patients with normal T scores this subgroup had a threefold higher fracture risk (22 vs. 69). s-PTH, s-Ca and 25[OH] vitamin D were all normal. Bone markers did not display major deviations from normal, but patients with OI type III displayed higher resorption marker levels than type I and IV. Multivariate regression analysis showed that only gender and total body BMD were significant determinants of fracture susceptibility, and the differences for total body BMC, BMD and Z scores were significant between the OI subtypes.
In adult OI, DXA measurements only identified few patients as osteoporotic. These patients, however, exhibited a much higher fracture propensity. Due to deformities, low body height and pre-existing fractures, DXA assessment is complicated in this disease, and further studies are needed to work out how to minimize the impact of these confounders.
Previous studies have confirmed that the prevalence of decreased bone mineral density is elevated in patients with inflammatory bowel disease. The objective of the current study was to determine the prevalence of osteopenia and osteoporosis in a cross-sectional outpatient population of 242 adult patients with Crohn's disease and to determine which clinical characteristics and serum and urine biochemical factors might be predictive of bone loss. Thirty-seven percent had normal bone density, 50.0% were osteopenic, and 12.9% were osteoporotic. Among the sites used to diagnose low bone mineral density, the femoral neck demonstrated the highest prevalence of osteopenia and the ultra-distal radius the highest prevalence of osteoporosis. However, low bone mineral density at one site was always predictive of low bone mineral density at the other. Corticosteroid use during the year before assessment was found to be consistently predictive of low bone mineral density in males but not in females. In contrast, low body mass index and high platelet counts were consistently predictive of low bone mineral density in females but not in males. Disease location, smoking, and age were not predictive of changes in bone mineral density.
We sought to investigate associations between central hemodynamic parameters (estimated from radial pulse wave analyses (PWAs)), cardiovascular disease (CVD), and albuminuria in type 1 diabetes.
We conducted an observational study of 636 type 1 diabetes patients. Central hemodynamics were measured by PWA as central aortic systolic pressure (CASP), central aortic pulse pressure (CPP), central aortic diastolic pressure (CADP), and subendocardial viability ratio (SEVR). CVD included revascularization, myocardial infarction, peripheral arterial disease, and stroke. Albuminuria was urinary albumin excretion rate =30 mg/24 hours. We computed standardized odds ratios (ORs) adjusted for sex, age, mean arterial pressure (MAP), heart rate, height, estimated glomerular filtration rate, glycated hemoglobin (HbA1c) total cholesterol, antihypertensive medication, and smoking. At follow-up, development of end-stage renal disease (ESRD) and mortality was traced through electronic medical records.
Patients were aged a mean of 54±13 years, and 289 (45%) were women. The mean ± SD was 118±17 mm Hg for CASP, 75±10 mm Hg for CADP, 43±14 mm Hg for CPP, and 150±32 for SEVR. In fully adjusted models, increased CASP and CPP and decreased CADP and SEVR were associated with presence of CVD (n = 132; P = 0.02) and presence of albuminuria (n = 335; P