Glyphosate exposure in pregnancy and shortened gestational length: a prospective Indiana birth cohort study.

BACKGROUND: Glyphosate (GLY) is the most heavily used herbicide worldwide but the extent of exposure in human pregnancy remains unknown. Its residues are found in the environment, major crops, and food items that humans, including pregnant women, consume daily. Since GLY exposure in pregnancy may also increase fetal exposure risk, we designed a birth-cohort study to determine exposure frequency, potential exposure pathways, and associations with fetal growth indicators and pregnancy length. METHOD: Urine and residential drinking water samples were obtained from 71 women with singleton pregnancies living in Central Indiana while they received routine prenatal care. GLY measurements were performed using liquid chromatography-tandem mass spectrometry. Demographic and survey information relating to food and water consumption, stress, and residence were obtained by questionnaire. Maternal risk factors and neonatal outcomes were abstracted from medical records. Correlation analyses were used to assess relationships of urine GLY levels with fetal growth indicators and gestational length. RESULTS: The mean age of participants was 29 years, and the majority were Caucasian. Ninety three percent of the pregnant women had GLY levels above the limit of detection (0.1 ng/mL). Mean urinary GLY was 3.40 ng/mL (range 0.5-7.20 ng/mL). Higher GLY levels were found in women who lived in rural areas (p = 0.02), and in those who consumed > 24 oz. of caffeinated beverages per day (p = 0.004). None of the drinking water samples had detectable GLY levels. We observed no correlations with fetal growth indicators such as birth weight percentile and head circumference. However, higher GLY urine levels were significantly correlated with shortened gestational lengths (r = - 0.28, p = 0.02). CONCLUSIONS: This is the first study of GLY exposure in US pregnant women using urine specimens as a direct measure of exposure. We found that > 90% of pregnant women had detectable GLY levels and that these levels correlated significantly with shortened pregnancy lengths. Although our study cohort was small and regional and had limited racial/ethnic diversity, it provides direct evidence of maternal GLY exposure and a significant correlation with shortened pregnancy. Further investigations in a more geographically and racially diverse cohort would be necessary before these findings could be generalized.

Coercion in the Evolution of Plant-Microbe Communication: A Perspective.

Plants and microbes are dependent on chemical signals as a means of interkingdom communication. There are two predicted paths for the evolution of these signals. Ritualization is the oft-assumed pathway for the evolution of plant-microbe communication systems. In this process, chemical signals, which benefit both receiver and sender, evolve from chemical cues, which benefit only the receiver. However, plant-microbe signaling may evolve from coercive interactions as well, a process known as sensory manipulation. Here, we aim to highlight the prevalence of coercive interactions and discuss sensory manipulation in the context of plant-microbe interactions. We present two examples of stabilized coercion: microbial coercion of plants via the release of phytohormones and plant coercion of microbes via manipulation of quorum-sensing compounds. Furthermore, we provide an evolutionary framework for the emergence of signaling from coercive plant-microbe interactions through the process of sensory manipulation. We hope that researchers will recognize the relevance of coercive interactions in plant-microbe systems and consider sensory manipulation as a plausible evolutionary trajectory for the emergence of plant-microbe signaling.

Estimating retrospective exposure of household humidifier disinfectants.

UNLABELLED: We conducted a comprehensive humidifier disinfectant exposure characterization for 374 subjects with lung disease who presumed their disease was related to humidifier disinfectant use (patient group) and for 303 of their family members (family group) for an ongoing epidemiological study. We visited the homes of the registered patients to investigate disinfectant use characteristics. Probability of exposure to disinfectants was determined from the questionnaire and supporting evidence from photographs demonstrating the use of humidifier disinfectant, disinfectant purchase receipts, any residual disinfectant, and the consistency of their statements. Exposure duration was estimated as cumulative disinfectant use hours from the questionnaire. Airborne disinfectant exposure intensity (µg/m(3)) was estimated based on the disinfectant volume (ml) and frequency added to the humidifier per day, disinfectant bulk level (µg/ml), the volume of the room (m(3)) with humidifier disinfectant, and the degree of ventilation. Overall, the distribution patterns of the intensity, duration, and cumulative exposure to humidifier disinfectants for the patient group were higher than those of the family group, especially for pregnant women and patients ≤6 years old. Further study is underway to evaluate the association between the disinfectant exposures estimated here with clinically diagnosed lung disease. PRACTICAL IMPLICATIONS: Retrospective exposure to household humidifier disinfectant as estimated here can be used to evaluate associations with clinically diagnosed lung disease due to the use of humidifier disinfectant in Korea. The framework, with modifications to account for dispersion and use patterns, can also be potentially adapted to assessment of other household chemical exposures.

Workplace measurements by the U.S. Occupational Safety and Health Administration since 1979: Descriptive analysis and potential uses for exposure assessment.

This letter summarizes modifications to the results presented in Lavoué et al. (2012): Lavoué, J., Burstyn, I.,Friesen, M. (2012) Workplace Measurements by the US Occupational Safety and Health Administration since1979: Descriptive Analysis and Potential Uses for Exposure Assessment. Annals of occupational hygiene57(1):77­97. Although several results were altered, the conclusions were not affected by the changes.

Workplace measurements by the US Occupational Safety and Health Administration since 1979: descriptive analysis and potential uses for exposure assessment.

BACKGROUND: Inspectors from the US Occupational Safety and Health Administration (OSHA) have been collecting industrial hygiene samples since 1972 to verify compliance with Permissible Exposure Limits. Starting in 1979, these measurements were computerized into the Integrated Management Information System (IMIS). In 2010, a dataset of over 1 million personal sample results analysed at OSHA's central laboratory in Salt Lake City [Chemical Exposure Health Data (CEHD)], only partially overlapping the IMIS database, was placed into public domain via the internet. We undertook this study to inform potential users about the relationship between this newly available OSHA data and IMIS and to offer insight about the opportunities and challenges associated with the use of OSHA measurement data for occupational exposure assessment. METHODS: We conducted a literature review of previous uses of IMIS in occupational health research and performed a descriptive analysis of the data recently made available and compared them to the IMIS database for lead, the most frequently sampled agent. RESULTS: The literature review yielded 29 studies reporting use of IMIS data, but none using the CEHD data. Most studies focused on a single contaminant, with silica and lead being most frequently analysed. Sixteen studies addressed potential bias in IMIS, mostly by examining the association between exposure levels and ancillary information. Although no biases of appreciable magnitude were consistently reported across studies and agents, these assessments may have been obscured by selective under-reporting of non-detectable measurements. The CEHD data comprised 1 450 836 records from 1984 to 2009, not counting analytical blanks and erroneous records. Seventy eight agents with >1000 personal samples yielded 1 037 367 records. Unlike IMIS, which contain administrative information (company size, job description), ancillary information in the CEHD data is mostly analytical. When the IMIS and CEHD measurements of lead were merged, 23 033 (39.2%) records were in common to both IMIS and CEHD datasets, 10 681 (18.2%) records were only in IMIS, and 25 012 (42.6%) records were only in the CEHD database. While IMIS-only records represent data analysed in other laboratories, CEHD-only records suggest partial reporting of sampling results by OSHA inspectors into IMIS. For lead, the percentage of non-detects in the CEHD-only data was 71% compared to 42% and 46% in the both-IMIS-CEHD and IMIS-only datasets, respectively, suggesting differential under-reporting of non-detects in IMIS. CONCLUSIONS: IMIS and the CEHD datasets represent the biggest source of multi-industry exposure data in the USA and should be considered as a valuable source of information for occupational exposure assessment. The lack of empirical data on biases, adequate interpretation of non-detects in OSHA data, complicated by suspected differential under-reporting, remain the principal challenges to the valid estimation of average exposure conditions. We advocate additional comparisons between IMIS and CEHD data and discuss analytical strategies that may play a key role in meeting these challenges.

Childhood exposure to sexual abuse and partnership outcomes at age 30.

BACKGROUND: In this study, 30-year longitudinal data from the Christchurch Health and Development Study (CHDS) were used to examine the associations between childhood exposure to sexual abuse and intimate relationship outcomes at age 30. In addition, a broad range of early childhood and family confounding factors were tested, and the role of intervening factors from adolescence was explored. METHOD: The investigation analyzed data from a birth cohort of over 900 New Zealand adults studied to the age of 30. At ages 18 and 21 cohort members reported on any exposure to sexual abuse prior to age 16. This information, along with prospective data gathered in childhood and adolescence, was used to predict partnership outcomes at age 30. RESULTS: After adjustment for early childhood and family factors, exposure to more severe forms of childhood sexual abuse (CSA) was associated with earlier and more frequent cohabitation, higher rates of perpetrated interpartner violence (IPV), and early parenthood, lower relationship satisfaction and investment. Several factors from adolescence partially or fully mediated these associations, notably a history of early consensual sexual intercourse, higher number of sexual partnerships, substance abuse problems, and self-esteem. After adjustment for intervening factors, exposure to CSA remained significantly associated with IPV. CONCLUSIONS: The findings support a causal chain process, whereby early childhood and family factors place some individuals at risk for CSA. The extent of CSA exposure is related to adolescent risk taking, which in turn leads to early and more frequent cohabitation, risk of IPV, and lower relationship satisfaction and investment.

Mixed infections may promote diversification of mutualistic symbionts: why are there ineffective rhizobia?

While strategy variation is a key feature of symbiotic mutualisms, little work focuses on the origin of this diversity. Rhizobia strategies range from mutualistic nitrogen fixers to parasitic nonfixers that hoard plant resources to increase their own survival in soil. Host plants reward beneficial rhizobia with higher nodule growth rates, generating a trade-off between reproduction in nodules and subsequent survival in soil. However, hosts might not discriminate between strains in mixed infections, allowing nonfixing strains to escape sanctions. We construct an adaptive dynamics model of symbiotic nitrogen-fixation and find general situations where symbionts undergo adaptive diversification, but in most situations complete nonfixers do not evolve. Social conflict in mixed infections when symbionts face a survival-reproduction trade-off can drive the origin of some coexisting symbiont strategies, where less mutualistic strains exploit benefits generated by better mutualists.

Successes and failures of Kadanoff-Baym dynamics in Hubbard nanoclusters.

We study the nonequilibrium dynamics of small, strongly correlated clusters, described by a Hubbard Hamiltonian, by propagating in time the Kadanoff-Baym equations within the Hartree-Fock, second Born, GW, and T-matrix approximations. We compare the results to exact numerical solutions. We find that the time-dependent T matrix is overall superior to the other approximations, and is in good agreement with the exact results in the low-density regime. In the long time limit, the many-body approximations attain an unphysical steady state which we attribute to the implicit inclusion of infinite-order diagrams in a few-body system.

Iatrogenic severe depression of high-density lipoprotein cholesterol.

The authors present 5 cases of paradoxical depression of high-density lipoprotein (HDL) cholesterol induced by fibrate drugs. In a 24-month review of all cases seen in one physician's practice at the Winnipeg Health Sciences Centre Lipid Clinic, 492 patients made a total of 1187 visits. Sixty-eight of them were given a fibrate drug (14%). Ten patients had HDL cholesterol levels that were less than 0.5 mmol/L (2%), and of these, 5 cases were due to exposure to fenofibrate (1%). These 5 cases comprised 7.4% of the 68 patients who were given any fibrate drug during that period. Mean levels were as follows: HDL cholesterol on fenofibrate 0.27, off fenofibrate 1.0 mmol/L and apo A1 on fenofibrate 0.41, off fenofibrate 1.17 g/L. A literature review revealed documented cases in 37 patients involving fibrates alone or in combination with other drugs known to cause decreased HDL cholesterol levels. In 13 patients, exposure was to fibrate therapy alone; in those exposed to combinations, the effect was clearly attributable to fibrates in 9; in 14, the nonfibrates (mostly rosiglitazone) were the attributable drugs; and in 1, it was impossible to tell. Thus, fibrate therapy should always be suspected as a cause of profoundly depressed HDL cholesterol.

Relationships between alumina and bauxite dust exposure and cancer, respiratory and circulatory disease.

OBJECTIVES: To examine the associations between alumina and bauxite dust exposure and cancer incidence and circulatory and respiratory disease mortality among bauxite miners and alumina refinery workers. METHODS: This cohort of 5770 males has previously been linked to national mortality and national and state cancer incidence registries (1983-2002). In this paper, Poisson regression was used to undertake internal comparisons within the cohort based on subgroups of cumulative exposure to inhalable bauxite and alumina dust. Exposure was estimated using job histories and historical air monitoring data. RESULTS: There was no association between ever bauxite exposure and any of the outcomes. There was a borderline significant association between ever alumina exposure and cerebrovascular disease mortality (10 deaths, RR 3.8, 95% CI 1.1 to 13). There was some evidence of an exposure-response relationship between cumulative bauxite exposure and non-malignant respiratory disease mortality (seven deaths, trend p value: 0.01) and between cumulative alumina exposure and cerebrovascular disease mortality (trend p value: 0.04). These associations were based on very few cases and for non-malignant respiratory disease the deaths represented a heterogeneous mixture of causes. There was no evidence of an excess risk for any cancer type with bauxite or alumina exposure. CONCLUSIONS: These preliminary findings, based on very few cases, suggest that cumulative inhalable bauxite exposure may be associated with an excess risk of death from non-malignant respiratory disease and that cumulative inhalable alumina dust exposure may be associated with an excess risk of death from cerebrovascular disease. Neither exposure appears to increase the risk of incident cancers.

Quantum chaos and regularity in ultracold Fermi gases.

Quantum fluctuation of the energy is studied for an ultracold gas of interacting fermions trapped in a three-dimensional potential. Periodic-orbit theory is explored, and energy fluctuations are studied versus the particle number for generic regular and chaotic systems, as well as for a system defined by a harmonic confinement potential. Temperature effects on the energy fluctuations are investigated.

Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition.

Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and alpha- and gamma-tocopherol, with the risk of gastric adenocarcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 countries. A secondary objective was to determine the association of total sum of carotenoids, retinol and alpha-tocopherol on GCs by anatomical subsite (cardia/noncardia) and histological subtype (diffuse/intestinal). Analytes were measured by high-performance liquid chromatography in prediagnostic plasma from 244 GC cases and 645 controls matched by age, gender, study centre and date of blood donation. Conditional logistic regression models adjusted by body mass index, total energy intake, smoking and Helicobacter pylori infection status were used to estimate relative cancer risks. After an average 3.2 years of follow-up, a negative association with GC risk was observed in the highest vs the lowest quartiles of plasma beta-cryptoxanthin (odds ratio (OR) = 0.53, 95% confidence intervals (CI) = 0.30-0.94, P(trend) = 0.006), zeaxanthin (OR = 0.39, 95% CI = 0.22-0.69, P(trend) = 0.005), retinol (OR = 0.55, 95% CI = 0.33-0.93, P(trend) = 0.005) and lipid-unadjusted alpha-tocopherol (OR = 0.59, 95% CI = 0.37-0.94, P(trend) = 0.022). For all analytes, no heterogeneity of risk estimates or significant associations were observed by anatomical subsite. In the diffuse histological subtype, an inverse association was observed with the highest vs lowest quartile of lipid-unadjusted alpha-tocopherol (OR = 0.26, 95% CI = 0.11-0.65, P(trend) = 0.003). These results show that higher plasma concentrations of some carotenoids, retinol and alpha-tocopherol are associated with reduced risk of GC.

From expert-based to quantitative retrospective exposure assessment at a Soderberg aluminum smelter.

OBJECTIVES: Expert judgement of exposure levels is often only poorly or moderately correlated with directly measured levels. For a follow-up of a historical cohort study at a Söderberg aluminum smelter we updated an expert-based semiquantitative job exposure matrix of coal tar pitch volatiles (CTPV) to quantitative estimates of CTPV and benzo(a)pyrene (BaP). METHODS: Mixed effects models to predict exposure for potroom operation and maintenance jobs were constructed from personal CTPV and BaP measurements. Mean exposures of jobs in non-potroom locations were directly calculated when measurements were available. Exposure estimates for jobs/time periods with no measurements were based on proportion of time spent in exposed areas compared to jobs where exposure was modeled or measured. For pre-1977, the original expert exposure assignments were calibrated using the updated 1977 estimates. RESULTS: The rate of change in exposure levels varied by time period and was accounted for in mixed models with a linear spline time trend. Other variables significant in the models were job, potroom group and season as fixed effects, and worker as a random effect. The models for potroom operations explained 45 and 27% of the variability in the CTPV and BaP measurements, respectively. The models for maintenance jobs explained 40 and 19% of the variability in the CTPV and BaP measurements, respectively. For 1977-2000 model estimates, direct calculation of means and extrapolation from modeled/measured exposures accounted for 57, 6 and 37% of the exposed person-years, respectively. CONCLUSIONS: The above methodology maximized the use of exposure measurements and largely replaced the original expert-based estimates. Finer discrimination between exposure levels was possible with the updated exposure assessment. The new estimates are expected to reduce exposure misclassification and help better assess the exposure-response relationships.

Predicting historical dust and wood dust exposure in sawmills: model development and validation.

Nonspecific dust measurements are used as a surrogate for wood dust exposure in sawmills. However, the wood dust component of dust has been found to vary by job and work area. Thus, the use of nonspecific dust exposure levels in epidemiologic studies may introduce exposure misclassification when assessing wood-related health effects. To improve exposure assessment in a retrospective cohort of 28,000 sawmill workers, we developed and evaluated the validity of two empirical models of exposure: one for nonspecific dust and one for wood dust. The dust model was constructed using 1,395 dust measurements collected in 13 sawmills for research or regulatory purposes from 1981 to 1997. Inter-sampler conversion factors were used to obtain inhalable dust equivalents if necessary. The wood dust model was constructed after applying adjustment factors to subtract nonwood components of the dust from the original measurements. The validity of the two models was tested against measurements (n = 213) from a technologically similar mill that was not part of the cohort study. The proportions of variability explained by the dust and wood dust models were 35% and 54%, respectively. When tested against the validation mill, the biases in the dust model were -33% for outdoor jobs and 2% for indoor jobs. The biases in the wood dust model were 2% for outdoor jobs and -3% for indoor jobs. Strong correlations were observed between the predicted and observed geometric means of jobs (0.79 and 0.70 for the dust model and wood dust model, respectively). Testing the validity of predictive models examines the generalizability of the models. The low overall bias, especially in the wood-specific model, increases our confidence in the use of these models for all sawmills to assess both nonspecific particulate and wood-related health effects in the historical cohort study.

Management of return-to-work programs for workers with musculoskeletal disorders: a qualitative study in three Canadian provinces.

In this qualitative research project, researchers in three Canadian provinces explored the perceptions of many different actors involved in return-to-work (RTW) programs for injured workers, studying their views on successful RTW strategies and barriers to/facilitators of the RTW process, then analyzing the underlying dynamics driving their different experiences. Each research team recruited actors in a variety of different workplaces and key informants in the RTW system, and used a combination of in-depth, semi-structured interviews and focus groups to collect data, which were coded using an open coding system. Analysis took a social constructionist perspective. The roles and mandates of the different groups of actors (injured workers; other workplace actors; actors outside the workplace), while sometimes complementary, could also differ, leading to tension and conflict. Characteristics of injured workers described as influencing RTW success included personal and sociodemographic factors, beliefs and attitudes, and motivation. Human resources managers and health care professionals tended to attribute workers' motivation to their individual characteristics, whereas injured workers, worker representatives and health and safety managers described workplace culture and the degree to which workers' well-being was considered as having a strong influence on workers' motivation. Some supervisors experienced role conflict when responsible for both production quotas and RTW programs, but difficulties were alleviated by innovations such as consideration of RTW program responsibilities in the determination of production quotas and in performance evaluations. RTW program success seemed related to labor-management relations and top management commitment to Health and Safety. Non-workplace issues included confusion stemming from the compensation system itself, communication difficulties with some treating physicians, and role conflict on the part of physicians wishing to advocate for patients whose problems were non-compensable. Several common themes emerged from the experiences related by the wide range of actors including the importance of trust, respect, communication and labor relations in the failure or success of RTW programs for injured workers.

Validation of a semi-quantitative job exposure matrix at a Söderberg aluminum smelter.

OBJECTIVES: We tested the validity of a job exposure matrix (JEM) for coal tar pitch volatiles (CTPV) at a Söderberg aluminum smelter. The JEM had been developed by a committee of company hygienists and union representatives for an earlier study of cancer incidence and mortality. Our aim was to test the validity and reliability of the expert-based assignments. METHODS: Personal CTPV exposure measurements (n = 1879) overlapped 11 yr of the JEM. The arithmetic mean was calculated for 35 job/time period combinations (35% of the exposed work history), categorized using the original exposure intervals, and compared with the expert-based assignments. RESULTS: The expert-based and the measurement-based exposure assignments were only moderately correlated (Spearman's rho = 0.42; weighted kappa = 0.39, CI 0.10-0.69). Only 40% of the expert-based medium category assignments were correctly assigned, with better agreement in the low (84%) and high (100%) categories. Pot operation jobs exhibited better agreement (rho = 0.60) than the maintenance and pot shell repair jobs (rho = 0.25). The mid-point value of the medium category was overestimated by 0.3 mg/m(3). CONCLUSIONS: The expert-based exposure assignments may be improved by better characterizing the transitions between exposure categories, by accounting for exposure differences between pot lines and by re-examining the category mid-point values used in calculating the cumulative exposure. Lack of historical exposure measurements often requires reliance on expert knowledge to assess exposure levels. Validating the experts' estimates against available exposure measurements may help to identify weaknesses in the exposure assessment where improvements may be possible, as was shown here.

Concentration of 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) in urine and alkali-hydrolyzed urine after consumption of charbroiled beef.

Heterocyclic amines (HAs) and polycyclic aromatic hydrocarbons are carcinogenic products formed during the cooking of meat at moderate to high temperatures. We have previously shown that the urinary concentration of 1-hydroxypyrene-glucuronide, a metabolite of pyrene, increased significantly in ten subjects who had ingested charbroiled ground beef. We now report the time course and interindividual variation of 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) concentration in the urine samples from these ten subjects. PhIP concentration was determined in both untreated and alkali-hydrolyzed urine to obtain estimates of the proportion of conjugated PhIP metabolites in each subject. PhIP was measured by gas chromatography-negative ion chemical ionization-mass spectrometry after derivatization with pentafluorobenzyl bromide. Ten healthy non-smoking males consumed identical amounts of broiled beef on five consecutive days. The morning after the first day of broiled beef consumption, urinary concentration of PhIP increased 14-38 fold above mean pre-feed concentration of PhIP in individual alkali-hydrolyzed urine samples. Following cessation of broiled beef consumption, urinary PhIP concentration declined to near pre-feed levels within 48-72 hrs. The ratio of total alkali-labile PhIP metabolites to unmetabolized PhIP varied by about 2.7-fold among subjects, ranging from 18:1 to 48:1, suggesting that interindividual differences in PhIP metabolism occur and can be detected by this method. This study of urinary PhIP following ingestion of meat cooked by charbroiling, that contains both HAs and polycyclic aromatic hydrocarbons, extends previous studies of ingestion of pan-fried meat that contains primarily HAs. The results indicate that significant amounts of PhIP are bioavailable from ingestion of charbroiled ground beef and that measurement of proportions of alkali-labile PhIP metabolites and parent PhIP in human urine may yield information on individual metabolism of ingested PhIP.

Chlorination of guanosine and other nucleosides by hypochlorous acid and myeloperoxidase of activated human neutrophils. Catalysis by nicotine and trimethylamine.

Activated human neutrophils secrete myeloperoxidase, which generates HOCl from H2O2 and Cl(-). We have found that various (2'-deoxy)nucleosides react with HOCl to form chlorinated (2'-deoxy)nucleosides, including novel 8-chloro(2'-deoxy)guanosine, 5-chloro(2'-deoxy)cytidine, and 8-chloro(2'-deoxy)adenosine formed in yields of 1.6, 1.6, and 0.2%, respectively, when 0.5 mM nucleoside reacted with 0.5 mM HOCl at pH 7.4. The relative chlorination, oxidation, and nitration activities of HOCl, myeloperoxidase, and activated human neutrophils in the presence and absence of nitrite were studied by analyzing 8-chloro-, 8-oxo-7,8-dihydro-, and 8-nitro-guanosine, respectively, using guanosine as a probe. 8-Chloroguanosine was always more easily formed than 8-oxo-7,8-dihydro- or 8-nitro-guanosine. Using electrospray ionization tandem mass spectrometry, we show that several chlorinated nucleosides including 8-chloro(2'-deoxy)guanosine are formed following exposure of isolated DNA or RNA to HOCl. Micromolar concentrations of tertiary amines such as nicotine and trimethylamine dramatically enhanced chlorination of free (2'-deoxy)nucleosides and nucleosides in RNA by HOCl. As the G-463A polymorphism of the MPO gene, which strongly reduces myeloperoxidase mRNA expression, is associated with a reduced risk of lung cancer, chlorination damage of DNA /RNA and nucleosides by myeloperoxidase and its enhancement by nicotine may be important in the pathophysiology of human diseases associated with tobacco habits.

Formation of spiroiminodihydantoin nucleoside by reaction of 8-oxo-7,8-dihydro-2'-deoxyguanosine with hypochlorous acid or a myeloperoxidase-H(2)O(2)-Cl(-) system.

Hypochlorous acid (HOCl), generated by myeloperoxidase from H(2)O(2) and Cl(-), is a strong chlorinating and oxidizing agent, playing an important role in host defense and inflammatory tissue injury. As several recent studies have shown that various oxidizing agents including peroxynitrite and singlet oxygen react readily with 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) to yield further oxidized products, we have studied the reaction of 8-oxodGuo with reagent HOCl and with a myeloperoxidase-H(2)O(2)-Cl(-) system. When 1 mM 8-oxodGuo was reacted with 0.5 mM HOCl at pH 7.4 and 37 degrees C, two major products were formed. They were identified as the diastereomers of spiroiminodihydantoin deoxyribonucleoside (dSph) on the basis of their identical ESI-MS and UV spectra and HPLC retention times with those of the major reaction products which were reported to be formed in other oxidation systems including potassium monopersulfate plus cobalt (II) chloride, peroxynitrite plus thiol, and type II photosensitization. Under the above reaction conditions, the yield of the diastereomers of dSph was 0.38 mM, with 0.57 mM 8-oxodGuo remaining unreacted. Since the presence of 50% D(2)O, 10 mM sodium azide, or 2% ethanol did not affect the yield of the products, involvement of singlet oxygen and hydroxyl radical in the formation of dSph from 8-oxodGuo with HOCl was ruled out. A 1000-fold excess of dGuo did not inhibit the reaction of 8-oxodGuo with HOCl, indicating that 8-oxodGuo reacts more readily than dGuo with HOCl. dSph was also formed by reaction of 8-oxodGuo with myeloperoxidase in the presence of H(2)O(2) and Cl(-). Our results suggest that formation of dSph from 8-oxodGuo is mediated, possibly via an addition of Cl(+) to, or two-electron oxidation of 8-oxodGuo, with HOCl or the myeloperoxidase-H(2)O(2)-Cl(-) system.

Canadian guidelines for cardiac rehabilitation and atherosclerotic heart disease prevention: a summary.

Atherosclerotic heart disease (AHD) is the leading cause of death in Canadian women and men. Cardiac rehabilitation has been repeatedly shown to reduce cardiac morbidity and mortality significantly among patients with documented AHD. The Canadian Association of Cardiac Rehabilitation (CACR) has defined cardiac rehabilitation as "the enhancement and maintenance of cardiovascular health through individualized programs designed to optimize physical, psychological, social, vocational and emotional status. This process includes the facilitation and delivery of secondary prevention through heart hazard (risk factor) identification and modification in an effort to prevent disease progression and the recurrence of cardiac events". This summary presents a limited amount of background information and the majority of clinical practice recommendations contained within the previously published CACR Guidelines. These evidence-based clinical recommendations are intended as guidelines to good clinical practice rather than as standards of care. The key focus of this summary is the need for complete and targeted intervention of all heart hazards in patients at high or very high risk for, or with documented, AHD. To achieve this goal, the CACR Guidelines and this summary present risk stratification strategies designed to determine unambiguously a patient's risk of exercise-related cardiac events (short term absolute risk or disease prognosis) and their risk of recurrent AHD events (long term absolute risk from disease progression). The establishment of the short term and long term absolute AHD risks can then be used to determine heart hazard targets and the type of exercise program prescribed for patients with AHD. Despite the use of evidence-based medical practices, none of the recommendations presented in this document can replace the expert judgment of properly trained and experienced cardiac rehabilitation professionals. Health care providers must always be free to choose where and when clinical practice guidelines are applied, modified or superceded, depending on individual patient circumstances.