Acute Illnesses and Injuries Related to Total Release Foggers - 10 States, 2007-2015.

Total release foggers (TRFs) (also known as "bug bombs") are pesticide products often used indoors to kill insects. After an earlier report found that TRFs pose a risk for acute illness (1), the Environmental Protection Agency required improved labels on TRFs manufactured after September 2012 (2). To examine the early impact of relabeling, the magnitude and characteristics of acute TRF-related illness were evaluated for the period 2007-2015. A total of 3,222 TRF-related illnesses were identified in 10 participating states, based on three data sources: Sentinel Event Notification System for Occupational Risk-Pesticides (SENSOR) programs, the California Department of Pesticide Regulation (CDPR) program, and poison control centers (PCCs) in Florida, Texas, and Washington. No statistically significant decline in the overall TRF-illness incidence rate was found. Failure to vacate treated premises during application was the most commonly reported cause of exposure. To reduce TRF-related illness, integrated pest management strategies (3) need to be adopted, as well as better communication about the hazards and proper uses of TRFs. Redesigning TRFs to prevent sudden, unexpected activation might also be useful.

Magnitude and characteristics of acute paraquat- and diquat-related illnesses in the US: 1998-2013.

BACKGROUND: Paraquat and diquat are among the most commonly used herbicides in the world. OBJECTIVES: Determine the magnitude, characteristics, and root causes for acute paraquat- and diquat-related illnesses in the US METHODS: Illnesses associated with paraquat or diquat exposure occurring from 1998 through 2011 were identified from the Sentinel Event Notification System for Occupational Risks (SENSOR)-Pesticides Program, the California Department of Pesticide Regulation (CDPR) Pesticide Illness Surveillance Program (PISP), and the Incident Data System (IDS). Cases identified by the National Poison Data System (NPDS) were reviewed for the years 1998-2003 and 2006-2013. RESULTS: A total of 300 paraquat- and 144 diquat-related acute illnesses were identified by SENSOR, PISP, and IDS. NPDS identified 693 paraquat- and 2128 diquat-related acute illnesses. In SENSOR/PISP/IDS, illnesses were commonly low severity (paraquat=41%; diquat=81%); however, SENSOR/PISP/IDS identified 24 deaths caused by paraquat and 5 deaths associated with diquat. Nineteen paraquat-related deaths were due to ingestion, seven of which were unintentional, often due to improper storage in beverage bottles. In SENSOR/PISP/IDS, paraquat and diquat-related acute illnesses were work-related in 68% (n=203) and 29% (n=42) of cases, respectively. When herbicide application site was known, the vast majority of acute paraquat-related illnesses (81%) arose from agricultural applications. Common root causes of illness were failure to use adequate personal protective equipment (PPE), application equipment failure, and spill/splash of herbicide. CONCLUSIONS: Although the magnitude of acute paraquat/diquat-related illnesses was relatively low, several fatalities were identified. Many illnesses could be prevented through stricter compliance with label requirements (e.g. ensuring proper herbicide storage and PPE use), and through enhanced training of certified applicators.

PKA-induced receptor activator of NF-kappaB ligand (RANKL) expression in vascular cells mediates osteoclastogenesis but not matrix calcification.

Vascular calcification is a predictor of cardiovascular mortality and is prevalent in patients with atherosclerosis and chronic renal disease. It resembles skeletal osteogenesis, and many bone cells as well as bone-related factors involved in both formation and resorption have been localized in calcified arteries. Previously, we showed that aortic medial cells undergo osteoblastic differentiation and matrix calcification both spontaneously and in response to PKA agonists. The PKA signaling pathway is also involved in regulating bone resorption in skeletal tissue by stimulating osteoblast-production of osteoclast regulating cytokines, including receptor-activator of nuclear κB ligand (RANKL) and interleukins. Therefore, we investigated whether PKA activators regulate osteoclastogenesis in aortic smooth muscle cells (SMC). Treatment of murine SMC with the PKA agonist forskolin stimulated RANKL expression at both mRNA and protein levels. Forskolin also stimulated expression of interleukin-6 but not osteoprotegerin (OPG), an inhibitor of RANKL. Consistent with these results, osteoclastic differentiation was induced when monocytic preosteoclasts (RAW264.7) were cocultured with forskolin-treated aortic SMC. Oxidized phospholipids also slightly induced RANKL expression in T lymphocytes, another potential source of RANKL in the vasculature. Because previous studies have shown that RANKL treatment alone induces matrix calcification of valvular and vascular cells, we next examined whether RANKL mediates forskolin-induced matrix calcification by aortic SMC. RANKL inhibition with OPG had little or no effect on osteoblastic differentiation and matrix calcification of aortic SMC. These findings suggest that, as in skeletal tissues, PKA activation induces bone resorptive factors in the vasculature and that aortic SMC calcification specifically induced by PKA, is not mediated by RANKL.

Bone density and hyperlipidemia: the T-lymphocyte connection.

Osteoporosis, which contributes to morbidity and mortality, often coexists with cardiovascular disease, especially atherosclerosis. We have reported recently that in vitro exposure of human T-lymphocytes to oxidized lipids induced expression of a key osteoclastogenic cytokine, receptor activator of NF-κB ligand (RANKL). Our previous studies have shown that mice fed an atherogenic high-fat diet developed osteopenia and that bone marrow preosteoclasts from these hyperlipidemic mice have increased osteoclastic potential. To investigate the role of T-lymphocytes in the diet-induced bone loss, C57BL/6 mice were fed either chow or a high-fat diet, and bone parameters and T-lymphocyte activation were assessed at 6 and 11 months. Consistent with our previous findings, peripheral quantitative computed tomographic (pQCT) analysis showed that mice in the high-fat group had lower bone mineral content than mice in the chow group. Furthermore, histomorphometric analysis showed decreased structural parameters in the high-fat group. Coculture studies showed that bone marrow cells isolated from the high-fat group, which contained increased levels of activated memory T-lymphocytes compared with bone marrow cells from the chow mice, supported osteoclastic differentiation of RAW 264.7 cells. Additionally, RANKL expression was upregulated significantly in the T-lymphocytes isolated from the bone marrow of the high-fat group. Splenic T-lymphocytes isolated from the high-fat group also had increased expression of transcripts for the receptor for oxidized lipids (LOX-1) as well as for inflammatory and osteoclastogenic cytokines, including RANKL, interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), IL-1ß, and interferon γ (IFN-γ). Together these findings suggest that T-lymphocytes play a key role in the osteoclastogenesis induced by a high-fat diet and may contribute to the bone loss associated with diet-induced osteopenia.

Oxidized lipids enhance RANKL production by T lymphocytes: implications for lipid-induced bone loss.

Osteoporosis is a systemic disease that is associated with increased morbidity, mortality and health care costs. Whereas osteoclasts and osteoblasts are the main regulators of bone homeostasis, recent studies underscore a key role for the immune system, particularly via activation-induced T lymphocyte production of receptor activator of NFkappaB ligand (RANKL). Well-documented as a mediator of T lymphocyte/dendritic cell interactions, RANKL also stimulates the maturation and activation of bone-resorbing osteoclasts. Given that lipid oxidation products mediate inflammatory and metabolic disorders such as osteoporosis and atherosclerosis, and since oxidized lipids affect several T lymphocyte functions, we hypothesized that RANKL production might also be subject to modulation by oxidized lipids. Here, we show that short term exposure of both unstimulated and activated human T lymphocytes to minimally oxidized low density lipoprotein (LDL), but not native LDL, significantly enhances RANKL production and promotes expression of the lectin-like oxidized LDL receptor-1 (LOX-1). The effect, which is also observed with 8-iso-Prostaglandin E2, an inflammatory isoprostane produced by lipid peroxidation, is mediated via the NFkappaB pathway, and involves increased RANKL mRNA expression. The link between oxidized lipids and T lymphocytes is further reinforced by analysis of hyperlipidemic mice, in which bone loss is associated with increased RANKL mRNA in T lymphocytes and elevated RANKL serum levels. Our results suggest a novel pathway by which T lymphocytes contribute to bone changes, namely, via oxidized lipid enhancement of RANKL production. These findings may help elucidate clinical associations between cardiovascular disease and decreased bone mass, and may also lead to new immune-based approaches to osteoporosis.