Michael E. Andrew

Mouse pulmonary dose- and time course-responses induced by exposure to multi-walled carbon nanotubes

Carbon nanotubes (CNT) come in a variety of types, but one of the most common forms is multi-walled carbon nanotubes (MWCNT). MWCNT have potential applications in many diverse commercial processes, and thus human exposures are considered to be likely. In order to investigate the pulmonary toxicity of MWCNT, we conducted an in vivo dose-response and time course study of MWCNT in mice in order to assess their ability to induce pulmonary inflammation, damage, and fibrosis using doses that approximate estimated human occupational exposures. MWCNT were dispersed in dispersion medium (DM) and male C57BL/6J mice (7 weeks old) received either DM (vehicle control), 10, 20, 40 or 80mug MWCNT by aspiration exposure. At 1, 7, 28 and 56 days post-exposure, MWCNT-induced pulmonary toxicity was investigated. Bronchoalveolar lavage (BAL) studies determined pulmonary inflammation and damage was dose-dependent and peaked at 7 days post-exposure. By 56 days post-exposure, pulmonary inflammation and damage markers were returning to control levels, except for the 40mug MWCNT dose, which was still significantly higher than vehicle control. Histopathological studies determined that MWCNT exposure caused rapid development of pulmonary fibrosis by 7 days post-exposure, that granulomatous inflammation persisted throughout the 56-day post-exposure period, and also demonstrated that MWCNT can reach the pleura after pulmonary exposure. In summary, the data reported here indicate that MWCNT exposure rapidly produces significant adverse health outcomes in the lung. Furthermore, the observation that MWCNT reach the pleura after aspiration exposure indicates that more extensive investigations are needed to fully assess if pleural penetration results in any adverse health outcomes.

Area Under the Curve and Other Summary Indicators of Repeated Waking Cortisol Measurements

Objective: To derive the area under the curve and related summary measures of stress from saliva samples collected over time and to provide insight into the interpretation of the derived parameters. In research designed to assess the health consequences of stress these samples are often used as a physiologic indicator of the responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis. To make these repeated measurements of salivary cortisol more useful in defining the relationships between stress and health there is a need to derive two forms of area under the curve that summarize the measurements: area under the curve with respect to ground (AUCG) and area under the curve with respect to increase (AUCI). The latter parameters, AUCI, however, is seldom used by research scientists. Methods: In this study, interpretation and generic definition of the area under the curve was provided through graphical analyses and examination of its association with other summary measures using data from the Buffalo Cardio-Metabolic Occupational Police Stress (BCOPS) Pilot Study. In generic form, AUCI is derived as the area under the curve above the baseline value minus the area above the curve below the baseline value. Results: The sign and magnitude of AUCI are related to the profile and the rate of change of the measurements over time. The parameter showed significant associations with other summary indicators that measure pattern or rate of change of the measurements over time. Conclusion: Principal components analyses revealed that summary parameters derived from repeated cortisol measurements can be grouped into two meaningful general categories: measures of the magnitude of response and measures of the pattern of response over time. AUCG = area under the curve with respect to ground; AUCI = area under the curve with respect to increase; AUCB = area under the curve with respect to baseline; HPA = hypothalamic-pituitary-adrenal; PCA = principal component analyses.

Body mass index and blood pressure in Korean men and women : the Korean National Blood Pressure Survey

Alms and methods The association between body mass index (BMI) and blood pressure is well known in relatively obese populations. The purpose of the present study was to investigate the relationship between BMI and blood pressure in a lean population. Through cluster sampling, individuals aged >30 years in 190 out of 154 082 districts were selected for study. Among 25 567 eligible individuals, measurements of blood pressure and BMI were made in 22 354. Results The BMI for males was 22.8 ± 2.7kg/m2 and for females was 23.4 ± 3.2 kg/m2 (means ± SD). Over a BMI range from 16 to 31 kg/m2 the relationships between BMI and systolic and diastolic blood pressure were almost linear. Over the BMI range 25–31 kg/m2 (overweight-to-obese) each BMI unit was associated with a difference of 1.0 mmHg in diastolic blood pressure. Over the BMI range 16–25 kg/m2 (normal-to-lean) each BMI unit was associated with a difference of 0.89 mmHg in diastolic blood pressure. Conclusion We conclude that a strong association between BMI and blood pressure exists for lean as well as for obese subjects.

Association of a Dietary Inflammatory Index With Inflammatory Indices and Metabolic Syndrome Among Police Officers

Objectives:To determine whether the dietary inflammatory index (DII) is associated with inflammatory or metabolic biomarkers and metabolic syndrome (MetSyn) among police officers. Methods:Cross-sectional data from the Buffalo Cardio-Metabolic Occupational Police Stress study were derived from saliva and fasting blood samples, anthropometric measurements, long-term shiftwork histories, and demographic, stress/depression, and food frequency questionnaires (FFQs). Metabolic syndrome was defined using standard criteria. Results:Officers in DII quartiles 2 to 4 were more likely to exceed a threshold of 3.0 mg/L for C-reactive protein (odds ratio [OR] = 1.88; 95% confidence interval [95% CI] = 1.02 to 3.45; OR = 2.17; 95% CI = 1.19 to 3.95; OR = 1.57; 95% CI = 0.85 to 2.88, respectively) compared with quartile 1. The glucose intolerance component of MetSyn was more prevalent among officers in DII quartile 4 than among those in quartile 1 (OR = 2.03; 95% CI = 1.08 to 3.82). Conclusions:A pro-inflammatory diet was associated with elevated CRP and with the glucose intolerance component of MetSyn.

Acute pulmonary dose–responses to inhaled multi-walled carbon nanotubes

Abstract This study investigated the in vivo pulmonary toxicity of inhaled multi-walled carbon nanotubes (MWCNT). Mice-inhaled aerosolized MWCNT (10 mg/m3, 5 h/day) for 2, 4, 8 or 12 days. MWCNT lung burden was linearly related to exposure duration. MWCNT-induced pulmonary inflammation was assessed by determining whole lung lavage (WLL) polymorphonuclear leukocytes (PMN). Lung cytotoxicity was assessed by WLL fluid LDH activities. WLL fluid albumin concentrations were determined as a marker of alveolar air–blood barrier integrity. These parameters significantly increased in MWCNT-exposed mice versus controls and were dose-dependent. Histopathologic alterations identified in the lung included (1) bronciolocentric inflammation, (2) bronchiolar epithelial hyperplasia and hypertrophy, (3) fibrosis, (4) vascular changes and (5) rare pleural penetration. MWCNT translocated to the lymph node where the deep paracortex was expanded after 8 or 12 days. Acute inhalation of MWCNT induced dose-dependent pulmonary inflammation and damage with rapid development of pulmonary fibrosis, and also demonstrated that MWCNT can reach the pleura after inhalation exposure.

Telomere Length, Current Perceived Stress, and Urinary Stress Hormones in Women

Telomeres are repetitive DNA sequences that cap and protect the ends of chromosomes; critically short telomeres may lead to cellular senescence or carcinogenic transformation. Previous findings suggest a link between psychosocial stress, shorter telomeres, and chronic disease risk. This cross-sectional study examined relative telomere length in relation to perceived stress and urinary stress hormones in a sample of participants (n = 647) in the National Institute of Environmental Health Sciences Sister Study, a cohort of women ages 35 to 74 years who have a sister with breast cancer. Average leukocyte telomere length was determined by quantitative PCR. Current stress was assessed using the Perceived Stress Scale and creatinine-adjusted neuroendocrine hormones in first morning urines. Linear regression models estimated differences in telomere length base pairs (bp) associated with stress measures adjusted for age, race, smoking, and obesity. Women with higher perceived stress had somewhat shorter telomeres [adjusted difference of −129bp for being at or above moderate stress levels; 95% confidence interval (CI), −292 to 33], but telomere length did not decrease monotonically with higher stress levels. Shorter telomeres were independently associated with increasing age (−27bp/year), obesity, and current smoking. Significant stress-related differences in telomere length were seen in women ages 55 years and older (−289bp; 95% CI, −519 to −59), those with recent major losses (−420bp; 95% CI, −814 to −27), and those with above-average urinary catecholamines (e.g., epinephrine: −484bp; 95% CI, −709 to −259). Although current perceived stress was only modestly associated with shorter telomeres in this broad sample of women, our findings suggest the effect of stress on telomere length may vary depending on neuroendocrine responsiveness, external stressors, and age. (Cancer Epidemiol Biomarkers Prev 2009;18(2):551–60)

Glia pathology in the prefrontal cortex in alcohol dependence with and without depressive symptoms

BACKGROUND Reductions in glial density and enlargement of glial nuclei have been reported in the dorsolateral prefrontal cortex (dlPFC) in mood disorders. In alcohol dependence, often comorbid with depression, it is unclear whether there are changes in the density and size of glial cells in the dlPFC. METHODS The packing density and size of Nissl-stained glial cell nuclei were analyzed postmortem in the cortical layers of the dlPFC from 21 control and 17 alcohol-dependent (Alc) subjects without Wernicke or Korsakoff syndromes. Eight Alc subjects had depressive symptoms. The density of glial cells was measured with a three-dimensional cell counting method, and the areal fraction of glial fibrillary acidic protein immunoreactivity (GFAP) was also determined. RESULTS Glial density was reduced by 11-14% in layers V and VI and in all layers combined in the Alc group. The size of glial nuclei was decreased by 3.2% in Alc subjects. The Alc subjects with depressive symptoms showed the lowest values of density and size. There was no difference in GFAP immunoreactivity, although the lowest values were in the Alc group. CONCLUSIONS Alcohol dependence is characterized by decreases in both density and size of glia in the dlPFC. Glial pathology may be more severe in Alc subjects with depressive symptoms.

Prevalence, Awareness, Treatment, and Control of Hypertension in the Jackson Heart Study

African Americans have higher reported hypertension prevalence and lower control rates than other ethnic groups in the United States. Hypertension prevalence, awareness, treatment, and control (outcomes) and potentially associated demographic, lifestyle, comorbidity, and health care access factors were examined in 5249 adult participants (3362 women and 1887 men) aged 21 to 94 years enrolled in the Jackson Heart Study. Hypertension prevalence (62.9%), awareness (87.3%), treatment (83.2%), and control (66.4%) were high. Control declined with advancing age; estimates for all of the outcomes were higher for women compared with men. Lower socioeconomic status was associated with prevalence and control. Smoking was negatively associated with awareness and treatment, particularly among men. Comorbidities (diabetes, chronic kidney disease, and cardiovascular disease), likely driven by the high rates of obesity, correlated with hypertension prevalence, awareness, treatment, and control. Lack of health insurance was marginally associated with poorer control, whereas use of preventive care was positively associated with prevalence, awareness, and treatment, particularly among men. In comparisons with the 1994–2004 National Health and Nutrition Examination Survey data adjusted to Jackson Heart Study sex, age, and socioeconomic status distribution, control rates among Jackson Heart Study participants appeared to be higher than in their national counterparts and similar to that of whites. These results suggest that public health efforts to increase awareness and treatment among African Americans have been relatively effective. The Jackson Heart Study data indicate that better control rates can be achieved in this high-risk population.

Atypical Work Hours and Metabolic Syndrome Among Police Officers

ABSTRACT This study examined whether atypical work hours are associated with metabolic syndrome among a random sample of 98 police officers. Shift work and overtime data from daily payroll records and reported sleep duration were obtained. Metabolic syndrome was defined as elevated waist circumference and triglycerides, low HDL cholesterol, hypertension, and glucose intolerance. Multivariate analysis of variance and analysis of covariance models were used for analyses. Officers working midnight shifts were on average younger and had a slightly higher mean number of metabolic syndrome components. Stratification on sleep duration and overtime revealed significant associations between midnight shifts and the mean number of metabolic syndrome components among officers with less sleep (p = .013) and more overtime (p = .007). Results suggest shorter sleep duration and more overtime combined with midnight shift work may be important contributors to the metabolic syndrome.

Metabolic Syndrome and Echocardiographic Left Ventricular Mass in Blacks The Atherosclerosis Risk in Communities (ARIC) Study

Background—The metabolic syndrome has been associated with cardiovascular disease, but few studies have examined its relationship with subclinical measures such as echocardiographic left ventricular (LV) mass. This relationship is likely to be of particular importance in blacks, in whom both the metabolic syndrome and LV hypertrophy are common. Methods and Results—Echocardiography, performed at 1 of 4 sites in the Atherosclerosis Risk in Communities (ARIC) Study, was used to assess LV dimensions in 1572 black women and men aged 49 to 75 years in 1993–1996. Participants were categorized by number of metabolic syndrome characteristics (hypertension, dyslipidemia [low HDL cholesterol or high triglycerides], and glucose intolerance). Age-adjusted mean LV mass indexed by height (g/m) increased in a stepwise gradient with increasing number of metabolic syndrome disorders (none, any 1, any 2, all 3) in both women and men (125.1, 143.9, 153.7, 169.3 and 130.5, 148.7, 160.8, 170.2, respectively; P<0.001, tests for trend). Associations were diminished slightly by adjustment for smoking, alcohol intake, and education; additional adjustment for waist circumference resulted in some attenuation, but associations remained statistically significant. Analyses focusing on components of LV mass revealed that posterior wall and interventricular septal thickness, but not LV chamber size, were significantly and independently associated in general with the number of metabolic syndrome disorders. Consistent with these findings, relative wall thickness was also associated with number of disorders. Associations were similar across age and central adiposity. Hypertension had a strong influence on LV mass with additional contributions from dyslipidemia and glucose intolerance; strong synergistic effects of the syndrome beyond its individual components were not observed. Conclusions—In this cross-sectional population-based study of black women and men, the degree of metabolic syndrome clustering was strongly related to LV mass and its wall thickness components. These associations are consistent with a possible influence of underlying factors such as insulin resistance or other vascular processes on myocardial thickening and not on chamber size.