The dominant road traffic particle sources are wear particles from the road and tire interface, and from vehicle brake pads. The aim of this work was to investigate the effect of road and brake wear particles on pulmonary function and biomarkers in isolated perfused rat lungs. Particles were sampled from the studded tire wear of three road pavements containing different rock materials in a road simulator; and from the wear of two brake pad materials using a pin-on-disk machine. Isolated rat lungs inhaled the coarse and fine fractions of the sampled particles resulting in an estimated total particle lung dose of 50 mu g. The tidal volume (TV) was measured during the particle exposure and the following 50 min. Perfusate and BALF were analyzed for the cytokines TNF, CXCL1 and CCL3. The TV of lungs exposed to rock materials was significantly reduced after 25 min of exposure compared to the controls, for quartzite already after 4 min. The particles of the heavy-duty brake pads had no effect on the TV. Brake particles resulted in a significant elevation of CXCL1 in the perfusate. Brake particles showed significant elevations of all three measured cytokines, and quartzite showed a significant elevation of TNF in BALF. The study shows that the toxic effect on lungs exposed to airborne particles can be investigated using measurements of tidal volume. Furthermore, the study shows that the choice of rock material in road pavements has the potential to affect the toxicity of road wear PM10.

High-density lipoprotein (HDL) is a circulating complex of lipids and proteins known primarily for its role in reverse cholesterol transport and consequent protection from atheroma. In spite of this, therapies aimed at increasing HDL concentration do not reduce the risk of cardiovascular disease (CVD), and as such focus has shifted towards other HDL functions protective of vascular health - including vasodilatory, anti-inflammatory, antioxidant and anti-thrombotic actions. It has been demonstrated that in disease states such as CVD and conditions of insulin resistance such as Type 2 diabetes mellitus (T2DM), HDL function is impaired owing to changes in the abundance and function of HDL-associated lipids and proteins, resulting in reduced vascular protection. However, the gold standard density ultracentrifugation technique used in the isolation of HDL also co-isolates extracellular vesicles (EVs). EVs are ubiquitous cell-derived particles with lipid bilayers that carry a number of lipids, proteins and DNA/RNA/miRNAs involved in cell-to-cell communication. EVs transfer their bioactive load through interaction with cell surface receptors, membrane fusion and endocytic pathways, and have been implicated in both cardiovascular and metabolic diseases - both as protective and pathogenic mediators. Given that studies using density ultracentrifugation to isolate HDL also co-isolate EVs, biological effects attributed to HDL may be confounded by EVs. We hypothesise that some of HDLs vascular protective functions in cardiovascular and metabolic disease may be mediated by EVs. Elucidating the contribution of EVs to HDL functions will provide better understanding of vascular protection and function in conditions of insulin resistance and potentially provide novel therapeutic targets for such diseases.

Objective Electrical neuromodulation by deep brain stimulation (DBS) is a well-established method for treatment of severe essential tremor (ET). The mechanism behind the tremor relieving effect remains largely unknown. Our aim of this study was to evaluate alterations in proteomics pre- and post-DBS in patients diagnosed with severe ET. Materials and Methods Ten right-handed ET patients were included in this study. Cerebrospinal fluid (CSF) was obtained by lumbar puncture preoperatively (N = 10) and six months postoperatively (N = 7). The samples were analyzed by high sensitive liquid chromatography tandem mass spectrometry. Results Twenty-two proteins were statistically significantly altered in the CSF of ET patients before and after DBS treatment. Downregulated proteins were involved in regulatory processes of protein activation, complement activation, humoral immune response as well as acute inflammatory response. The upregulated proteins were involved in pathways for cell secretion, adhesion as well as response to axon injury. Conclusions DBS in ET patients effects the neurochemical environment in the CSF. These findings further elucidate the mechanisms of DBS and may lead to new biomarkers for evaluating the effect of DBS treatment.

Background

Production of crystal glass and colored art glassware have been going on in the south-eastern part of Sweden since the 1700s, at over 100 glassworks and smaller glass blowing facilities, resulting in environmental contamination with mainly arsenic (As), cadmium (Cd), lead (Pb) and polycyclic hydrocarbons (PAH). High levels of metals have been found in soil, and moderately elevated levels in vegetables, mushrooms and berries collected around the glassworks sites compared with reference areas. Food in general, is the major exposure source to metals, such as Cd and Pb, and PAHs. Exposure to these toxic metals and PAH has been associated with a variety of adverse health effects in humans including cancer.

Objective

The aim of the present study was to evaluate the occurrence of cancer in a cohort from the contaminated glasswork area in relation to long-term dietary intake of locally produced foods, while taking into account residential, occupational and life styles factors.

Methods

The study population was extracted from a population cohort of 34,266 individuals who, at some time between the years 1979–2004, lived within a 2 km radius of a glassworks or glass landfill. Register information on cancer incidence and questionnaire information on consumption of local foods (reflecting 30 years general eating habits), life-time residence in the area, life style factors and occupational exposure was collected. Furthermore, blood (n = 660) and urine (n = 400) samples were collected in a subsample of the population to explore associations between local food consumption frequencies, biomarker concentrations in blood (Cd, Pb, As) and urine (PAH metabolite 1-OHPy) as well as environmental and lifestyle factors. The concurrent exposure to persistent organic pollutants (POPs) from food was also considered. A case-control study was performed for evaluation of associations between intakes of local food and risk of cancer.

Results

Despite high environmental levels of Cd, Pb and As at glasswork sites and landfills, current metal exposure in the population living in the surrounding areas was similar or only moderately higher in our study population compared to the general population. Reported high consumption of certain local foods was associated with higher Cd and Pb, but not As, concentrations in blood, and 1-OHPy in urine. An increased risk of cancer was associated with smoking, family history of cancer, obesity, and residence in glasswork area before age 5 years. Also, a long-term high consumption of local foods (reflecting 30 years general eating habits), i.e. fish and meat (game, chicken, lamb), was associated with increased risk of various cancer forms.

Conclusions

The associations between consumption of local food and different types of cancer may reflect a higher contaminant exposure in the past, and thus, if consumption of local food contributes to the risk of acquiring cancer, that contribution is probably lower today than before. Furthermore, it cannot be ruled out that other contaminants in the food contribute to the increased cancer risks observed.

There is a strong association between periodontal disease and atherosclerotic cardiovascular disorders. A key event in the development of atherosclerosis is accumulation of modified lipoproteins within the arterial wall. We hypothesise that patients with periodontitis have an altered lipoprotein profile towards an atherogenic form. Therefore, the present study aims at identifying modifications of plasma lipoproteins in periodontitis. Lipoproteins from ten female patients with periodontitis and gender- and age-matched healthy controls were isolated by density-gradient ultracentrifugation. Proteins were separated by 2D gel-electrophoresis and identified by map-matching or by nano-LC followed by MS. Apolipoprotein (Apo) A-I (ApoA-I) methionine oxidation, Oxyblot, total antioxidant capacity and a multiplex of 71 inflammation-related plasma proteins were assessed. Reduced levels of apoJ, phospholipid transfer protein, apoF, complement C3, paraoxonase 3 and increased levels of alpha-1-antichymotrypsin, apoA-II, apoC-III were found in high-density lipoprotein (HDL) from the patients. In low-density lipoprotein (LDL)/very LDL (VLDL), the levels of apoL-1 and platelet-activating factor acetylhydrolase (PAF-AH) as well as apo-B fragments were increased. Methionine oxidation of apoA-I was increased in HDL and showed a relationship with periodontal parameters. alpha-1 antitrypsin and alpha-2-HS glycoprotein were oxidised in LDL/VLDL and antioxidant capacity was increased in the patient group. A total of 17 inflammation-related proteins were important for group separation with the highest discriminating proteins identified as IL-21, Fractalkine, IL-17F, IL-7, IL-1RA and IL-2. Patients with periodontitis have an altered plasma lipoprotein profile, defined by altered protein levels as well as post-translational and other structural modifications towards an atherogenic form, which supports a role of modified plasma lipoproteins as central in the link between periodontal and cardiovascular disease (CVD).

Particle exposure has been linked to an increased incidence of cardiovascular disease. Furthermore, particle exposure has been shown to have a chronic inhibitory effect on lung development in young people and may result in increased respiratory problems in adults or children with respiratory-related diseases. In today’s urban environments, particle levels are mainly monitored gravimetrically; however, other factors such as particle size, shape and surface reactivity have recently been noted as highly important in relation to possible health outcomes. Here, particles from TEOM monitor filters placed in three different cities were studied. The purpose of the study was to investigate whether there are variations in particle masses, cadmium and lead contents, as well as endotoxin levels between locations and time points over the year and if this can be correlated to the particles ability to induce a pro-inflammatory response in vitro. Results showed that it is possible to detect variations at different locations and at different time points over the year and that cadmium, lead and endotoxin levels did not coincide with the increased total particle masses while endotoxin levels coincided with pro-inflammatory responses in vitro. The present study shows that filter analysis is a useful complement to gravimetric or particle-counting measurements in studies of particle-related health effects and will give useful information regarding future air quality measurements.

BACKGROUND: Bariatric surgery has been shown to reduce cardiovascular events and cause specific mortality for coronary artery disease in obese patients. Lipoprotein biomarkers relating to low-density lipoprotein (LDL), high-density lipoprotein (HDL), their subfractions, and macrophage cholesterol efflux have all been hypothesized to be of value in cardiovascular risk assessment. OBJECTIVES: The objective of this study was to examine the effect of a lifestyle intervention followed by bariatric surgery on the lipid profile of morbidly obese patients. METHODS: Thirty-four morbidly obese patients were evaluated before and after lifestyle changes and then 1 year after bariatric surgery. They were compared with 17 lean subjects. Several lipoprotein metrics, serum amyloid A (SAA), serum paraoxonase-1 (PON1), and macrophage cholesterol efflux capacity (CEC) were assessed. RESULTS: Average weight loss after the lifestyle intervention was 10.5% and 1 year after bariatric surgery was 33.9%. The lifestyle intervention significantly decreased triglycerides (TGs; 28.7 mg/dL, P amp;lt; .05), LDL cholesterol (LDL-C; 32.3 mg/dL, P amp;lt; .0001), and apolipoprotein B (apoB; 62.9 mu g/mL, P amp;lt; .001). Bariatric surgery further reduced TGs (-36.7 mg/dL, P amp;lt; .05), increased HDL cholesterol (+12 mg/dL, P amp;lt; .0001), and reductions in LDL-C and apoB were sustained. Bariatric surgery reduced large, buoyant LDL (P amp;lt; .0001), but had no effect on the small, dense LDL.The large HDL subfractions increased (P amp;lt; .0001), but there was no effect on the smaller HDL sub fractions. The ratio for SAA/PON1 was reduced after the lifestyle intervention (P amp;lt; .01) and further reduced after bariatric surgery (P amp;lt; .0001). Neither the lifestyle intervention nor bariatric surgery had any effect on CEC. CONCLUSIONS: Lifestyle intervention followed by bariatric surgery in 34 morbidly obese patients showed favorable effects on TGs, LDL-C, and apoB. HDL cholesterol and apoA1 was increased, apoB/apoA1 ratio as well as SAA/PON1 ratio reduced, but bariatric surgery did not influence CEC. (C) 2017 National Lipid Association. All rights reserved.

Background: Epidemiological studies have shown that many welders experience respiratory symptoms. During the welding process a large number of airborne nanosized particles are generated, which might be inhaled and deposited in the respiratory tract. Knowledge of the underlying mechanisms behind observed symptoms is still partly lacking, although inflammation is suggested to play a central role. The aim of this study was to investigate the effects of welding fume particle exposure on the proteome expression level in welders suffering from respiratory symptoms, and changes in protein mediators in nasal lavage samples were analyzed. Such mediators will be helpful to clarify the pathomechanisms behind welding fume particle-induced effects. Methods: In an exposure chamber, 11 welders with work-related symptoms in the lower airways during the last month were exposed to mild-steel welding fume particles (1 mg/m(3)) and to filtered air, respectively, in a double-blind manner. Nasal lavage samples were collected before, immediately after, and the day after exposure. The proteins in the nasal lavage were analyzed with two different mass spectrometry approaches, label-free discovery shotgun LC-MS/MS and a targeted selected reaction monitoring LC-MS/MS analyzing 130 proteins and four in vivo peptide degradation products. Results: The analysis revealed 30 significantly changed proteins that were associated with two main pathways; activation of acute phase response signaling and activation of LXR/RXR, which is a nuclear receptor family involved in lipid signaling. Connective tissue proteins and proteins controlling the degradation of such tissues, including two different matrix metalloprotease proteins, MMP8 and MMP9, were among the significantly changed enzymes and were identified as important key players in the pathways. Conclusion: Exposure to mild-steel welding fume particles causes measurable changes on the proteome level in nasal lavage matrix in exposed welders, although no clinical symptoms were manifested. The results suggested that the exposure causes an immediate effect on the proteome level involving acute phase proteins and mediators regulating lipid signaling Proteases involved in maintaining the balance between the formation and degradation of extracellular matrix proteins are important key proteins in the induced effects.

Background and Objective: Several studies have shown an association between periodontitis and cardiovascular disease (CVD). Atherosclerosis is the major cause of CVD, and a key event in the development of atherosclerosis is accumulation of lipoproteins within the arterial wall. Bacteria are the primary etiologic agents in periodontitis and Porphyromonas gingivalis is the major pathogen in the disease. Several studies support a role of modified low-density lipoprotein (LDL) in atherogenesis; however, the pathogenic stimuli that induce the changes and the mechanisms by which this occur are unknown. This study aims to identify alterations in plasma lipoproteins induced by the periodontopathic species of bacterium, P.gingivalis, in vitro. Material and Methods: Plasma lipoproteins were isolated from whole blood treated with wild-type and gingipain-mutant (lacking either the Rgp- or Kgp gingipains) P.gingivalis by density/gradient-ultracentrifugation and were studied using 2-dimensional gel electrophoresis followed by matrix-assisted laser desorption/ionization mass spectrometry. Porphyromonasgingivalis-induced lipid peroxidation and antioxidant levels were measured by thiobarbituric acid-reactive substances and antioxidant assay kits, respectively, and lumiaggregometry was used for measurement of reactive oxygen species (ROS) and aggregation. Results: Porphyromonas gingivalis exerted substantial proteolytic effects on the lipoproteins. The Rgp gingipains were responsible for producing 2 apoE fragments, as well as 2 apoB-100 fragments, in LDL, and the Kgp gingipain produced an unidentified fragment in high-density lipoproteins. Porphyromonasgingivalis and its different gingipain variants induced ROS and consumed antioxidants. Both the Rgp and Kgp gingipains were involved in inducing lipid peroxidation. Conclusion: Porphyromonas gingivalis has the potential to change the expression of lipoproteins in blood, which may represent a crucial link between periodontitis and CVD.

Bisphenol A (BPA), is an artificial estrogen initially produced for medical purposes but is today widely used in polycarbonate plastics and epoxy resins. Exposure-related reproductive disorders have been found, but recently it has also been suggested that BPA may be involved in obesity, diabetes, myocardial hypertrophy and myocardial infarction in humans. To mimic a modern lifestyle, female rats were fed with fructose or fructose plus BPA (0.25mg/L drinking water). The myocardial left ventricle proteome of water controls, fructose-fed and fructose-fed plus BPA supplemented rats was explored. The proteome was investigated using nano-liquid chromatography tandem mass spectrometry and two-dimensional gel electrophoresis followed by matrix assisted laser desorption/ionization mass spectrometry identification. In total, 41 proteins were significantly altered by BPA exposure compared to water or fructose controls. Principal component analysis and cellular process enrichment analysis of altered proteins suggested increased fatty acid transport and oxidation, increased ROS generation and altered structural integrity of the myocardial left ventricle in the fructose-fed BPA-exposed rats, indicating unfavorable effects on the myocardium. In conclusion, BPA exposure in the rats induces major alterations in the myocardial proteome.