Effect of Dietary cis and trans fatty acids on serum lipoprotein[a] levels in humans

Serum lipoprotein[a] (Lp[a]) is a strong risk factor for coronary heart disease. We therefore examined the effect of dietary fatty acid composition on serum Lp[a] levels in three strictly controlled experiments with healthy normocholesterolemic men and women. In Expt. I, 58 subjects consumed a control diet high in saturated fatty acids for 17 days. For the next 36 days, 6.5% of total energy intake from saturated fatty acids was replaced by monounsaturates plus polyunsaturates (monounsaturated fatty acid diet; n = 29) or by polyunsaturates alone (polyunsaturated fatty acid diet; n = 29). Both diets caused a slight, nonsignificant, increase in median Lp[a] levels, with no difference between diets. In Expt. II, 10% of energy from the cholesterol-raising saturated fatty acids (lauric, myristic, and palmitic acid) was replaced by oleic acid or by trans-monounsaturated fatty acids. Each of the 59 participants received each diet for 3 weeks in random order. The median level of Lp[a] was 26 mg/l on the saturated fatty acid diet; it increased to 32 mg/l (P less than 0.020) on the oleic acid diet and to 45 mg/l (P less than 0.001) on the trans-fatty acid diet. The difference in Lp[a] between the trans-fatty acid and the oleic acid diets was also highly significant (P less than 0.001). Expt. III involved 56 subjects; all received 8% of energy from stearic acid, from linoleic acid, or from trans-monounsaturates, for 3 weeks each. All other nutrients were equal.

Neighborhood social and physical environment and general practitioner assessed morbidity

The aim of our study was to investigate the association between health enhancing and threatening, and social and physical aspects of the neighbourhood environment and general practitioner (GP) assessed morbidity of the people living there, in order to find out whether the effects of environmental characteristics add up or modify each other. We combined GP electronic health records with environmental data on neighbourhoods in the Netherlands. Cross-classified logistic multilevel models show the importance of taking into account several environmental characteristics and confounders, as social capital effects on the prevalence of morbidity disappear when other area characteristics are taken into account. Stratification by area socio-economic status, shows that the association between environmental characteristics and the prevalence of morbidity is stronger for people living in low SES areas. In low SES areas, green space seems to alleviate effects of air pollution on the prevalence of high blood pressure and diabetes, while the effects of green space and social capital reinforce each other

Quantitative assessment of airborne exposures generated during common cleaning tasks: a pilot study

Background: A growing body of epidemiologic evidence suggests an association between exposure to cleaning products with asthma and other respiratory disorders. Thus far, these studies have conducted only limited quantitative exposure assessments. Exposures from cleaning products are difficult to measure because they are complex mixtures of chemicals with a range of physicochemical properties, thus requiring multiple measurement techniques. We conducted a pilot exposure assessment study to identify methods for assessing short term, task-based airborne exposures and to quantitatively evaluate airborne exposures associated with cleaning tasks simulated under controlled work environment conditions. Methods: Sink, mirror, and toilet bowl cleaning tasks were simulated in a large ventilated bathroom and a small unventilated bathroom using a general purpose, a glass, and a bathroom cleaner. All tasks were performed for 10 minutes. Airborne total volatile organic compounds (TVOC) generated during the tasks were measured using a direct reading instrument (DRI) with a photo ionization detector. Volatile organic ingredients of the cleaning mixtures were assessed utilizing an integrated sampling and analytic method, EPA TO-17. Ammonia air concentrations were also measured with an electrochemical sensor embedded in the DRI. Results: Average TVOC concentrations calculated for 10 minute tasks ranged 0.02 - 6.49 ppm and the highest peak concentrations observed ranged 0.14-11 ppm. TVOC time concentration profiles indicated that exposures above background level remained present for about 20 minutes after cessation of the tasks. Among several targeted VOC compounds from cleaning mixtures, only 2-BE was detectable with the EPA method. The ten minute average 2- BE concentrations ranged 0.30 -21 ppm between tasks. The DRI underestimated 2-BE exposures compared to the results from the integrated method. The highest concentration of ammonia of 2.8 ppm occurred during mirror cleaning. Conclusions: Our results indicate that airborne exposures from short-term cleaning tasks can remain in the air even after tasks' cessation, suggesting potential exposures to anyone entering the room shortly after cleaning. Additionally, 2-BE concentrations from cleaning could approach occupational exposure limits and warrant further investigation. Measurement methods applied in this study can be useful for workplace assessment of airborne exposures during cleaning, if the limitations identified here are addressed

Respiratory symptoms and occupation: a cross-sectional study of the general population

BACKGROUND: This study focused on respiratory symptoms due to occupational exposures in a contemporary general population cohort. Subjects were from the Dutch Monitoring Project on Risk Factors for Chronic Diseases (MORGEN). The composition of this population enabled estimation of respiratory risks due to occupation from the recent past for both men and women. METHODS: The study subjects (aged 20–59) were all inhabitants of Doetinchem, a small industrial town, and came from a survey of a random sample of 1104 persons conducted in 1993. A total of 274 cases with respiratory symptoms (subdivided in asthma and bronchitis symptoms) and 274 controls without symptoms were matched for age and sex. Relations between industry and occupation and respiratory symptoms were explored and adjusted for smoking habits and social economic status. RESULTS: Employment in the 'construction' (OR = 3.38; 95%CI 1.02 – 11.27), 'metal' (OR = 3.17; 95%CI 0. 98 – 10.28), 'rubber, plastics and synthetics' (OR = 6.52; 95%CI 1.26 – 53.80), and 'printing' industry (OR = 3.96; 95%CI 0.85 – 18.48) were positively associated with chronic bronchitis symptoms. In addition, the 'metal' industry was found to be weakly associated with asthma symptoms (OR = 2.59; 95%CI 0.87 – 7.69). Duration of employment within these industries was also positively associated with respiratory symptoms. CONCLUSION: Respiratory symptoms in the general population are traceable to employment in particular industries even in a contemporary cohort with relatively young individuals

Occupation, smoking, and chronic obstructive respiratory disorders: a cross sectional study in an industrial area of Catalonia, Spain

BACKGROUND: Few studies have investigated the independent effects of occupational exposures and smoking on chronic bronchitis and airflow obstruction. We assessed the association between lifetime occupational exposures and airflow obstruction in a cross-sectional survey in an urban-industrial area of Catalonia, Spain. METHODS: We interviewed 576 subjects of both sexes aged 20–70 years (response rate 80%) randomly selected from census rolls, using the ATS questionnaire. Forced spirometry was performed by 497 subjects according to ATS normative. RESULTS: Lifetime occupational exposure to dust, gases or fumes was reported by 52% of the subjects (63% in men, 41% in women). Textile industry was the most frequently reported job in relation to these exposures (39%). Chronic cough, expectoration and wheeze were more prevalent in exposed subjects with odds ratios ranging from 1.7 to 2.0 being highest among never-smokers (2.1 to 4.3). Lung function differences between exposed and unexposed subjects were dependent on duration of exposure, but not on smoking habits. Subjects exposed more than 15 years to dusts, gases or fumes had lower lung function values (FEV(1 )-80 ml, 95% confidence interval (CI) -186 to 26; MMEF -163 ml, CI -397 to 71; FEV(1)/FVC ratio -1.7%, CI -3.3 to -0.2) than non-exposed. CONCLUSION: Chronic bronchitis symptoms and airflow obstruction are associated with occupational exposures in a population with a high employment in the textile industry. Lung function impairment was related to the duration of occupational exposure, being independent of the effect of smoking

Use of Activity-Based Probes to Develop High Throughput Screening Assays That Can Be Performed in Complex Cell Extracts

Background: High throughput screening (HTS) is one of the primary tools used to identify novel enzyme inhibitors. However, its applicability is generally restricted to targets that can either be expressed recombinantly or purified in large quantities. Methodology and Principal Findings: Here, we described a method to use activity-based probes (ABPs) to identify substrates that are sufficiently selective to allow HTS in complex biological samples. Because ABPs label their target enzymes through the formation of a permanent covalent bond, we can correlate labeling of target enzymes in a complex mixture with inhibition of turnover of a substrate in that same mixture. Thus, substrate specificity can be determined and substrates with sufficiently high selectivity for HTS can be identified. In this study, we demonstrate this method by using an ABP for dipeptidyl aminopeptidases to identify (Pro-Arg)2-Rhodamine as a specific substrate for DPAP1 in Plasmodium falciparum lysates and Cathepsin C in rat liver extracts. We then used this substrate to develop highly sensitive HTS assays (Z’.0.8) that are suitable for use in screening large collections of small molecules (i.e.300,000) for inhibitors of these proteases. Finally, we demonstrate that it is possible to use broad-spectrum ABPs to identify target-specific substrates. Conclusions: We believe that this approach will have value for many enzymatic systems where access to large amounts o

Interaction of atopy and smoking on respiratory effects of occupational dust exposure: a general population-based study

BACKGROUND: For individual exposures, effect modification by atopy or smoking has been reported on the occurrence of occupational airway disease. It is unclear if effect modification can be studied in a general population by an aggregated exposure measure. Assess relationship between airway obstruction and occupational exposure using a job-exposure-matrix (JEM) classifying jobs into 3 broad types of exposure, and test for effect modification by atopy, and smoking. METHODS: Data from 1,906 subjects were analyzed, all participants of the European Community Respiratory Health Survey. Job titles were categorized by an a priori constructed job exposure matrix into three classes of exposure to respectively organic dust, mineral dust, and gases/ fumes. Relationships were assessed for 'current wheeze', bronchial hyperresponsiveness (BHR), 'current asthma' (wheeze+BHR), and 'chronic bronchitis' (morning phlegm or morning cough), and lung function. RESULTS: Subjects with organic dust exposure in their work environment more frequently had 'current asthma' (OR 1.48, 95% C.I. 0.95;2.30), and a lower FEV(1 )(-59 mL, 95% C.I. -114;-4). The relationship was only present in asthmatic workers, and their risk was four-fold greater than in subjects with either atopy or exposure alone. Mineral dust exposure was associated with 'chronic bronchitis' (OR 2.22, 95% C.I. 1.16;4.23) and a lower FEV(1)/FVC ratio (-1.1%, 95% C.I. -1.8;-0.3). We observed an excess risk in smokers, greater than the separate effects of smoking or mineral dust exposure together. CONCLUSION: Occupational exposure to organic dust is associated with an increased risk of asthma, particularly in atopics. Chronic bronchitis occurs more frequently among individuals exposed to mineral dust, and smoking doubles this risk

The relation between paracetamol use and asthma:a GA2LEN European case-control study

Studies from the UK and USA suggest that frequent use of paracetamol (acetaminophen) may increase the risk of asthma, but data across Europe are lacking. As part of a multicentric case-control study organised by the Global Allergy and Asthma European Network (GA(2)LEN), it was examined whether or not frequent paracetamol use is associated with adult asthma across Europe. The network compared 521 cases with a diagnosis of asthma and reporting of asthma symptoms within the last 12 months with 507 controls with no diagnosis of asthma and no asthmatic symptoms within the last 12 months across 12 European centres. All cases and controls were selected from the same population, defined by age (2045 yrs) and place of residence. In a random effects meta-analysis, weekly use of paracetamol, compared with less frequent use, was strongly positively associated with asthma after controlling for confounders. There was no evidence for heterogeneity across centres. No association was seen between use of other analgesics and asthma. These data add to the increasing and consistent epidemiological evidence implicating frequent paracetamol use in asthma in diverse populations