Acute and longer-term cardiovascular conditions in the Deepwater Horizon Oil Spill Coast Guard Cohort.

INTRODUCTION: In 2010, the U.S. Coast Guard (USCG) led a clean-up response to the Deepwater Horizon (DWH) oil spill. Human studies evaluating acute and longer-term cardiovascular conditions associated with oil spill-related exposures are sparse. Thus, we aimed to investigate prevalent and incident cardiovascular symptoms/conditions in the DHW Oil Spill Coast Guard Cohort. METHODS: Self-reported oil spill exposures and cardiovascular symptoms were ascertained from post-deployment surveys (n = 4,885). For all active-duty cohort members (n = 45,193), prospective cardiovascular outcomes were classified via International Classification of Diseases, 9th Edition from military health encounter records up to 5.5 years post-DWH. We used log-binomial regression to calculate adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) in the cross-sectional analyses and Cox Proportional Hazards regression to calculate adjusted hazard ratios (aHR) and 95% CIs for incident cardiovascular diagnoses during 2010-2015 and stratifying by earlier (2010-2012) and later (2013-2015) time periods. RESULTS: Prevalence of chest pain was associated with increasing levels of crude oil exposure via inhalation (aPRhigh vs. none = 2.00, 95% CI = 1.16-3.42, p-trend = 0.03) and direct skin contact (aPRhigh vs. none = 2.72, 95% CI = 1.30-5.16, p-trend = 0.03). Similar associations were observed for sudden heartbeat changes and for being in the vicinity of burning oil exposure. In prospective analyses, responders (vs. non-responders) had an elevated risk for mitral valve disorders during 2013-2015 (aHR = 2.12, 95% CI = 1.15-3.90). Responders reporting ever (vs. never) crude oil inhalation exposure were at increased risk for essential hypertension, particularly benign essential hypertension during 2010-2012 (aHR = 2.00, 95% CI = 1.08-3.69). Responders with crude oil inhalation exposure also had an elevated risk for palpitations during 2013-2015 (aHR = 2.54, 95% CI = 1.36-4.74). Cardiovascular symptoms/conditions aPR and aHR estimates were generally stronger among responders reporting exposure to both crude oil and oil dispersants than among those reporting neither. CONCLUSIONS: In this large study of the DWH oil spill USCG responders, self-reported spill clean-up exposures were associated with acute and longer-term cardiovascular symptoms/conditions.

Engineered silica nanoparticles act as adjuvants to enhance allergic airway disease in mice.

BACKGROUND: With the increase in production and use of engineered nanoparticles (NP; ≤ 100 nm), safety concerns have risen about the potential health effects of occupational or environmental NP exposure. Results of animal toxicology studies suggest that inhalation of NP may cause pulmonary injury with subsequent acute or chronic inflammation. People with chronic respiratory diseases like asthma or allergic rhinitis may be even more susceptible to toxic effects of inhaled NP. Few studies, however, have investigated adverse effects of inhaled NP that may enhance the development of allergic airway disease. METHODS: We investigated the potential of polyethylene glycol coated amorphous silica NP (SNP; 90 nm diameter) to promote allergic airway disease when co-exposed during sensitization with an allergen. BALB/c mice were sensitized by intranasal instillation with 0.02% ovalbumin (OVA; allergen) or saline (control), and co-exposed to 0, 10, 100, or 400 µg of SNP. OVA-sensitized mice were then challenged intranasally with 0.5% OVA 14 and 15 days after sensitization, and all animals were sacrificed a day after the last OVA challenge. Blood and bronchoalveolar lavage fluid (BALF) were collected, and pulmonary tissue was processed for histopathology and biochemical and molecular analyses. RESULTS: Co-exposure to SNP during OVA sensitization caused a dose-dependent enhancement of allergic airway disease upon challenge with OVA alone. This adjuvant-like effect was manifested by significantly greater OVA-specific serum IgE, airway eosinophil infiltration, mucous cell metaplasia, and Th2 and Th17 cytokine gene and protein expression, as compared to mice that were sensitized to OVA without SNP. In saline controls, SNP exposure did cause a moderate increase in airway neutrophils at the highest doses. CONCLUSIONS: These results suggest that airway exposure to engineered SNP could enhance allergen sensitization and foster greater manifestation of allergic airway disease upon secondary allergen exposures. Whereas SNP caused innate immune responses at high doses in non-allergic mice, the adjuvant effects of SNP were found at lower doses in allergic mice and were Th2/Th17 related. In conclusion, these findings in mice suggest that individuals exposed to SNP might be more prone to manifest allergic airway disease, due to adjuvant-like properties of SNP.

Comparative anticonvulsant efficacy in the corneal kindled mouse model of partial epilepsy: Correlation with other seizure and epilepsy models.

Chronic electrical stimulation via corneal electrodes can rapidly yield large numbers of kindled mice with a seizure phenotype reflective of secondarily generalized partial seizures. The corneal kindled mouse model has been found to be a highly sensitive and efficient screening model for antiepileptic drug (AED) discovery. The present study further evaluates the utility of the corneal kindled mouse model as a tool for rapid screening of investigational AEDs. Results obtained with nine AEDs (valproic acid, lamotrigine, phenytoin, carbamazepine, levetiracetam, vigabatrin, topiramate, tiagabine, and ezogabine) with varying mechanisms of action and clinical spectrums, as well as six investigational compounds were evaluated in the corneal kindled mouse. ED(50) values are compared to those obtained in the hippocampal kindled rat, the mouse maximal electroshock (MES) model, the 6Hz partial psychomotor seizure model, and the subcutaneous pentylenetetrazol (scPTZ) test. The results obtained in the corneal kindled mouse demonstrate a positive correlation with those attained employing established preclinical models: MES (r² = 0.9511), scPTZ (r² = 0.9697), 6Hz (r² = 0.9519), and hippocampal kindling (r² = 0.9037). The demonstrated predictive ability of the corneal kindled mouse model supports its use in the early evaluation of investigational AEDs.