The pulmonary system represents a unique lipidomic environment as it contains cellular membrane-bound lipid species and a specialized reservoir of lipids in the airway epithelial lining fluid. As a major initial point of defense, airway lipids react to inhaled contaminants such as volatile organic compounds, oxides of nitrogen, or ozone (O), creating lipokine signaling that is crucial for both the initiation and resolution of inflammation within the lung. Dietary modulation of eicosanoids has gained increased attention in recent years for improvements to cardiovascular health.
View Article and Find Full Text PDFRising global concentrations of environmental micro- and nanoplastics (MNPs) drive concerns for human exposure and health outcomes. Applying pyrolysis gas chromatography-mass spectrometry (Py-GC/MS) methods to isolate and quantify MNPs from human samples, we compared MNP accumulation in kidneys, livers, and brains. Autopsy samples from the Office of the Medical Investigator in Albuquerque, NM, collected in 2016 and in 2024, were digested for Py-GC/MS analysis of 12 polymers.
View Article and Find Full Text PDFThe contribution of air pollution induced cardio-pulmonary damage on the development of hypertensive disorders of pregnancy and other adverse outcomes of pregnancy has gained increased attention as epidemiological data continues to highlight spatiotemporal pregnancy trends related to air pollution exposure. However clinical mechanistic data surrounding gestational complications remains sparse, necessitating the need for the use of animal models to study these types of complications of pregnancy. The current study seeks to examine the real-time effects of mid-gestational ozone exposure on maternal blood pressure and body temperature through the use of radiotelemetry in a rat model.
View Article and Find Full Text PDFThe exponential increase in global plastic usage has led to the emergence of nano- and microplastic (NMP) pollution as a pressing environmental issue due to its implications for human and other mammalian health. We have developed methodologies to extract solid materials from human tissue samples by saponification and ultracentrifugation, allowing for highly specific and quantitative analysis of plastics by pyrolysis-gas chromatography and mass spectrometry (Py-GC-MS). As a benchmark, placenta tissue samples were analyzed using fluorescence microscopy and automated particle count, which demonstrated the presence of >1-micron particles and fibers, but not nano-sized plastic particles.
View Article and Find Full Text PDFUnlabelled: Wildland fires have become progressively more extensive over the past 30 years in the US, and now routinely generate smoke that deteriorates air quality for most of the country. We explored the neurometabolomic impact that smoke derived from biomass has on older (18 months) female C57BL/6J mice, both acutely and after 10 weeks of recovery from exposures. Mice (N=6/group) were exposed to wood smoke (WS) 4 hours/day, every other day, for 2 weeks (7 exposures total) to an average concentration of 0.
View Article and Find Full Text PDFOzone (O3) is a criteria air pollutant with the most frequent incidence of exceeding air quality standards. Inhalation of O3 is known to cause lung inflammation and consequent systemic health effects, including endothelial dysfunction. Epidemiologic data have shown that gestational exposure to air pollutants correlates with complications of pregnancy, including low birth weight, intrauterine growth deficiency, preeclampsia, and premature birth.
View Article and Find Full Text PDFSmoke from wildland fires has been shown to produce neuroinflammation in preclinical models, characterized by neural infiltrations of neutrophils and monocytes, as well as altered neurovascular endothelial phenotypes. To address the longevity of such outcomes, the present study examined the temporal dynamics of neuroinflammation and metabolomics after inhalation exposures from biomass-derived smoke. 2-month-old female C57BL/6 J mice were exposed to wood smoke every other day for 2 weeks at an average exposure concentration of 0.
View Article and Find Full Text PDFEpidemiological studies have established that exposure to tungsten increases the risk of developing cardiovascular diseases. However, no studies have investigated how tungsten affects cardiac function or the development of cardiovascular disease. Inhalation of tungsten particulates is relevant in occupational settings, and inhalation of particulate matter has a known causative role in driving cardiovascular disease.
View Article and Find Full Text PDFSmoke from wildland fires has been shown to produce neuroinflammation in preclinical models, characterized by neural infiltrations of neutrophils and monocytes, as well as altered neurovascular endothelial phenotypes. To address the longevity of such outcomes, the present study examined the neuroinflammatory and metabolomic temporal dynamics after inhalation exposures from biomass-derived smoke. 2-month-old female C57BL/6J mice were exposed to wood smoke every other day for two weeks at an average exposure concentration of 0.
View Article and Find Full Text PDFMicroplastics represent an emerging environmental contaminant, with large gaps in our understanding of human health impacts. Furthermore, environmental factors may modify the plastic chemistry, further altering the toxic potency. Ultraviolet (UV) light is one such unavoidable factor for airborne microplastic particulates and a known modifier of polystyrene surface chemistry.
View Article and Find Full Text PDFUtilizing a mobile laboratory located >300 km away from wildfire smoke (WFS) sources, this study examined the systemic immune response profile, with a focus on neuroinflammatory and neurometabolomic consequences, resulting from inhalation exposure to naturally occurring wildfires in California, Arizona, and Washington in 2020. After a 20-day (4 h/day) exposure period in a mobile laboratory stationed in New Mexico, WFS-derived particulate matter (WFPM) inhalation resulted in significant neuroinflammation while immune activity in the peripheral (lung, bone marrow) appeared to be resolved in C57BL/6 mice. Importantly, WFPM exposure increased cerebrovascular endothelial cell activation and expression of adhesion molecules (VCAM-1 and ICAM-1) in addition to increased glial activation and peripheral immune cell infiltration into the brain.
View Article and Find Full Text PDFJ Am Pharm Assoc (2003)
May 2022
Background: Atrial fibrillation (AF) increases the risk of stroke. It can be asymptomatic and patients may be unaware they have AF. Therefore, there is a need to develop a sustainable community model to screen for unrecognized AF.
View Article and Find Full Text PDFHepatic drug-metabolizing enzymes (DMEs) play critical roles in determining the pharmacokinetics and pharmacodynamics of numerous therapeutic agents. As such, noninvasive biomarkers capable of predicting DME expression in the liver have the potential to be used to personalize pharmacotherapy and improve drug treatment outcomes. In the present study, we quantified carboxylesterase 1 (CES1) protein concentrations in plasma samples collected during a methylphenidate pharmacokinetics study.
View Article and Find Full Text PDFAims: Enalapril is a prodrug and needs to be activated by carboxylesterase 1 (CES1). A previous in vitro study demonstrated the CES1 genetic variant, G143E (rs71647871), significantly impaired enalapril activation. Two previous clinical studies examined the impact of G143E on single-dose enalapril PK (10 mg); however, the results were inconclusive.
View Article and Find Full Text PDFTrandolapril, an angiotensin-converting enzyme inhibitor prodrug, needs to be activated by carboxylesterase 1 (CES1) in the liver to exert its intended therapeutic effect. A previous in vitro study demonstrated that the CES1 genetic variant G143E (rs71647871) abolished CES1-mediated trandolapril activation in cells transfected with the variant. This study aimed to determine the effect of the G143E variant on trandolapril activation in human livers and the pharmacokinetics (PKs) and pharmacodynamics (PDs) in human subjects.
View Article and Find Full Text PDFCurr Pharm Teach Learn
March 2021
Introduction: This descriptive survey study was designed to collect specific data about intervention and remediation approaches used by schools and colleges of pharmacy (S/COPs) to meet the requirements of the Accreditation Council for Pharmacy Education Standard 17.
Methods: An electronic survey was developed and sent to all members of the American Association of Colleges of Pharmacy Curriculum and Student Services Personnel Special Interest Groups. The survey gathered details about institutional criteria and practices used in identification of students at risk of failure, steps of early intervention, and approaches to academic remediation.
Exposure to air pollutants such as ozone (O3) is associated with adverse pregnancy outcomes, including higher incidence of gestational hypertension, preeclampsia, and peripartum cardiomyopathy; however, the underlying mechanisms of this association remain unclear. We hypothesized that O3 exposures during early placental formation would lead to more adverse cardiovascular effects at term for exposed dams, as compared with late-term exposures. Pregnant Sprague Dawley rats were exposed (4 h) to either filtered air (FA) or O3 (0.
View Article and Find Full Text PDFThousands of abandoned uranium mines (AUMs) exist in the western United States. Due to improper remediation, windblown dusts generated from AUMs are of significant community concern. A mobile inhalation lab was sited near an AUM of high community concern ("Claim 28") with three primary objectives: to (1) determine the composition of the regional ambient particulate matter (PM), (2) assess meteorological characteristics (wind speed and direction), and (3) assess immunological and physiological responses of mice after exposures to concentrated ambient PM (or CAPs).
View Article and Find Full Text PDFBackground: Individuals with unrecognized atrial fibrillation (AF) may be at an increased risk of stroke. There is a need to develop a sustainable and reproducible population-based screening model to identify unrecognized AF.
Objective: The objective of this study is to evaluate AF screening and education at student pharmacist-driven health fairs.
Roadside proximity and exposure to mixed vehicular emissions (MVE) have been linked to adverse pulmonary and vascular outcomes. However, because of the complex nature of the contribution of particulate matter (PM) versus gases, it is difficult to decipher the precise causative factors regarding PM and the copollutant gaseous fraction. To this end, C57BL/6 and apolipoprotein E knockout mice (ApoE) were exposed to either filtered air (FA), fine particulate (FP), FP+gases (FP+G), ultrafine particulate (UFP), or UFP+gases (UFP+G).
View Article and Find Full Text PDFAmbient particulate matter (PM) is associated with increased mortality and morbidity, an effect influenced by the metal components of the PM. We characterized five sediment samples obtained near a tungsten-molybdenum ore-processing complex in Zakamensk, Russia for elemental composition and PM toxicity with regard to pulmonary, vascular, and neurological outcomes. Elemental and trace metals analysis of complete sediment and PM (the respirable fraction, < 10 µm mass mean aerodynamic diameter) were performed using inductively coupled plasma optical emission spectrometry (ICP-OES) and mass spectrometry (ICP-MS).
View Article and Find Full Text PDFPurpose: Ranolazine is a novel anti-angina treatment approved in the United States for chronic stable angina. Ranolazine pharmacokinetics have not been studied previously in patients who receive maintenance hemodialysis. This study describes the pharmacokinetics of ranolazine and three major metabolites (CVT-2738, CVT-2512, CVT-2514) in patients receiving thrice weekly hemodialysis.
View Article and Find Full Text PDFAlthough the microbiota in the proximal gastrointestinal (GI) tract have been implicated in health and disease, much about these microbes remains understudied compared to those in the distal GI tract. This study characterized the microbiota across multiple proximal GI sites over time in healthy individuals. As part of a study of the pharmacokinetics of oral mesalamine administration, healthy, fasted volunteers ( = 8; 10 observation periods total) were orally intubated with a four-lumen catheter with multiple aspiration ports.
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