Search

Exposure to wildfire smoke is associated with both acute and chronic cardiopulmonary illnesses, which are of special concern for wildland firefighters who experience repeated exposure to wood smoke. It is necessary to better understand the underlying pathophysiology by which wood smoke exposure increases pulmonary disease burdens in this population. We hypothesize that wood smoke exposure produces pulmonary dysfunction, lung inflammation, and gene expression profiles associated with future pulmonary complications. Male Long-Evans rats were intermittently exposed to smoldering eucalyptus wood smoke at 2 concentrations, low (11.0 ± 1.89 mg/m3) and high (23.7 ± 0.077 mg/m3), over a 2-week period. Whole-body plethysmography was measured intermittently throughout. Lung tissue and lavage fluid were collected 24 h after the final exposure for transcriptomics and metabolomics. Increasing smoke exposure upregulated neutrophils and select cytokines in the bronchoalveolar lavage fluid. In total, 3446 genes were differentially expressed in the lungs of rats in the high smoke exposure and only 1 gene in the low smoke exposure (Cd151). Genes altered in the high smoke group reflected changes to the Eukaryotic Initiation Factor 2 stress and oxidative stress responses, which mirrored metabolomics analyses. xMWAS-integrated analysis revealed that smoke exposure significantly altered pathways associated with oxidative stress, lung morphogenesis, and tumor proliferation pathways. These results indicate that intermittent, 2-week exposure to eucalyptus wood smoke leads to transcriptomic and metabolic changes in the lung that may predict future lung disease development. Collectively, these findings provide insight into cellular signaling pathways that may contribute to the chronic pulmonary conditions observed in wildland firefighters. [ABSTRACT FROM AUTHOR]

Inhalation of smoke from the burning of waste materials on military bases is associated with increased incidences of cardiopulmonary diseases. This study examined the respiratory and inflammatory effects of acute inhalation exposures in mice to smoke generated by military burn pit-related materials including plywood (PW), cardboard (CB), mixed plastics (PL), and a mixture of these three materials (MX) under smoldering (0.84 MCE) and flaming (0.97 MCE) burn conditions. Mice were exposed nose-only for one hour on two consecutive days to whole or filtered smoke or clean air alone. Smoldering combustion emissions had greater concentrations of PM (∼40 mg/m3) and VOCs (∼5–12 ppmv) than flaming emissions (∼4 mg/m3 and ∼1–2 ppmv, respectively); filtered emissions had equivalent levels of VOCs with negligible PM. Breathing parameters were assessed during exposure by head-out plethysmography. All four smoldering burn pit emission types reduced breathing frequency (F) and minute volumes (MV) compared with baseline exposures to clean air, and HEPA filtration significantly reduced the effects of all smoldering materials except CB. Flaming emissions had significantly less suppression of F and MV compared with smoldering conditions. No acute effects on lung inflammatory cells, cytokines, lung injury markers, or hematology parameters were noted in smoke-exposed mice compared with air controls, likely due to reduced respiration and upper respiratory scrubbing to reduce the total deposited PM dose in this short-term exposure. Our data suggest that material and combustion type influences respiratory responses to burn pit combustion emissions. Furthermore, PM filtration provides significant protective effects only for certain material types. [ABSTRACT FROM AUTHOR]

Recent epidemiological findings link asthma to adverse cardiovascular responses. Yet, the precise cardiovascular impacts of asthma have been challenging to disentangle from the potential cardiovascular effects caused by asthma medication. The purpose of this study was to determine the impacts of allergic airways disease alone on cardiovascular function in an experimental model. Female Wistar rats were intranasally sensitized and then challenged once per week for 5 weeks with saline vehicle or a mixture of environmental allergens (ragweed, house dust mite, and Aspergillus fumigatus). Ventilatory and cardiovascular function, measured using double-chamber plethysmography and implantable blood pressure (BP) telemetry and cardiovascular ultrasound, respectively, were assessed before sensitization and after single and final allergen challenge. Responses to a single 0.5 ppm ozone exposure and to the cardiac arrhythmogenic agent aconitine were also assessed after final challenge. A single allergen challenge in sensitized rats increased tidal volume and specific airways resistance in response to provocation with methacholine and increased bronchoalveolar lavage fluid (BALF) eosinophils, neutrophils, lymphocytes, cytokines interleukin (IL)-4, IL-5, IL-10, IL-1β, tumor necrosis factor-α, and keratinocyte chemoattract-growth-related oncogene characteristic of allergic airways responses. Lung responses after final allergen challenge in sensitized rats were diminished, although ozone exposure increased BALF IL-6, IL-13, IL-1 β, and interferon-γ and modified ventilatory responses only in the allergen group. Final allergen challenge also increased systolic and mean arterial BP, stroke volume, cardiac output, end-diastolic volume, sensitivity to aconitine-induced cardiac arrhythmia, and cardiac gene expression with lesser effects after a single challenge. These findings demonstrate that allergic airways responses may increase cardiovascular risk in part by altering BP and myocardial function and by causing cardiac electrical instability. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop a 12-week multicomponent, depression prevention pilot intervention and evaluate its feasibility and preliminary effects on improving levels and correlates of depressive symptoms, including anger, self-esteem perceived stress, social support, and racism. A quasi-experimental, mixed-methods design and a community-based participatory research (CBPR) approach was employed. University faculty, students and community residents collaborated at a low-income housing complex in a low-resourced, urban community. Fifteen low-income, ethnic minority mothers ages 23–46 years completed the intervention and evaluation surveys. Eight mothers participated in a focus group. The intervention included social group-dance, health education, and socialization. t -Tests, sign-tests, and thematic analysis was employed. Mothers identified barriers and facilitators of program engagement. Depressive symptoms were significantly reduced (t (14) = 2.41, p =.030). Self-esteem (t (14) = 2.28, p =.039) and social support levels (M = 4.5, p =.035) were significantly increased. This multicomponent intervention is feasible. Preliminary efficacy evidence was mixed. [ABSTRACT FROM AUTHOR]

This study identified coping and sociodemographic correlates and predictors of depressive symptoms in mothers at risk for clinical depression. A descriptive, cross-sectional design was employed. A convenience sample of 88 low-income or ethnic-minority mothers aged 21 to 45 completed a depression scale, demographic data sheet, and responded to an open-ended question. Content analysis, descriptive, and inferential statistics was used for data analysis. Exactly 42.5% of mothers reported high depressive symptoms (>16). Lower income levels (r =.342, p =.01) and head-of-household status (r =.220, p =.04) were significantly associated with higher depressive symptoms. Those who used social support coping had lower depressive symptoms than those who did not (t = 2.50, p =.014). Those using emotion-focused coping only had higher depressive symptoms than those using a mix of coping strategies (t = 2.60, p =.011). Healthcare providers can employ vigilant depression screening and encourage utilization of a mix of problem and emotion-focused coping strategies to reduce depressive symptoms and prevent clinical depression. [ABSTRACT FROM AUTHOR]

Honey bees and other wild bee species including bumble bees have experienced population declines in recent decades. Although many stressors are implicated in bee population declines, much attention has focused on neonicotinoid pesticides, which are widely used and known to be toxic to pollinators. One neonicotinoid, acetamiprid, has been studied very little in bumble bees, despite its use on bumble bee–pollinated crops. We assessed the impacts of acetamiprid to the North American bumble bee Bombus impatiens using the microcolony model. We examined nest growth, development, and subsequent nest productivity as measured by drone production. We found that high concentrations of acetamiprid in pollen (4520 µg/kg) significantly impacted nest growth, development, and, ultimately, reproduction (drone production). We found the no‐observable–adverse effect level to be 45.2 µg/kg. Overall, acetamiprid has the potential to negatively impact reproductive endpoints for B. impatiens. However, effects occurred at concentrations substantially higher than expected environmental concentrations that would be achieved when following label rates. Further work is required to assess the effects of this pesticide on B. impatiens via alternate routes of exposure and on queenright colonies. Environ Toxicol Chem 2020;39:2560–2569. © 2020 SETAC. This article has been contributed to by US Government employees and their work is in the public domain in the USA. [ABSTRACT FROM AUTHOR]

Worldwide, many pollinator populations are in decline. Population reductions have been documented for the agriculturally important honey bee (Apis mellifera), and other bee species such as bumble bees that are also critical for pollinating crops and natural landscapes. A variety of factors contribute to the observed population reductions, including exposure to agrochemicals. In recent decades, neonicotinoid pesticide use has dramatically increased, as have concerns regarding the safety of these chemicals for pollinator health. Here we assessed the toxicity of the neonicotinoid acetamiprid to the bumble bee Bombus impatiens, a species commercially available for use in agricultural settings in North America. Using the microcolony model, we examined nest growth, development and subsequent nest productivity as measured by drone production. We found that high concentrations of acetamiprid in syrup (11,300 μg/L) significantly impacted nest growth and development, and ultimately drone production, and exposure to 1,130 μg/L acetamiprid also significantly decreased drone production. The no observable adverse effect level was 113 μg/L. Overall, acetamiprid delivered in syrup can negatively impact B. impatiens nest development and productivity, however only at concentrations above which would be expected in the environment when used according to label rates. [ABSTRACT FROM AUTHOR]

Background: The physiological mechanisms underlying the development of respiratory hypersensitivity to cisplatin (CDDP) are not well-understood. It has been suggested that these reactions are likely the result of type I hypersensitivity, but other explanations are plausible and the potential for CDDP to induce type I hypersensitivity responses has not been directly evaluated in an animal model. Objectives and Methods: To investigate CDDP hypersensitivity, mice were topically sensitized through application of CDDP before being challenged by oropharyngeal aspiration (OPA) with CDDP. Before and immediately after OPA challenge, pulmonary responses were assessed using whole body plethysmography (WBP). Results: CDDP did not induce an immediate response or alter the respiratory rate in sensitized mice. Two days later, baseline enhanced pause (Penh) values were significantly elevated (p < 0.05) in mice challenged with CDDP. When challenged with methacholine (Mch) aerosol, Penh values were significantly elevated (p < 0.05) in sensitized mice and respiratory rate was reduced (p < 0.05). Lymph node cell counts and immunoglobulin E levels also indicated successful sensitization to CDDP. Irrespective of the sensitization state of the mice, the number of neutrophils increased significantly in bronchoalveolar lavage fluid (BALF) following CDDP challenge. BALF from sensitized mice also contained 2.46 (±0.8) × 104 eosinophils compared to less than 0.48 (±0.2) × 104 cells in non-sensitized mice (p < 0.05). Conclusions: The results from this study indicate that dermal exposure to CDDP induces immunological changes consistent with type I hypersensitivity and that a single respiratory challenge is enough to trigger pulmonary responses in dermally sensitized mice. These data provide previously unknown insights into the mechanisms of CDDP hypersensitivity. [ABSTRACT FROM AUTHOR]

Implantation is a sensitive window in reproductive development during which disruptions may increase the risk of adverse pregnancy outcomes including intrauterine growth restriction. Ozone exposure during implantation in rats reduces fetal weight near the end of gestation, potentially though impaired trophoblast migration and invasion and altered implantation. The current study characterized changes in ventilation, pulmonary injury, and circulating factors including hormonal, inflammatory, and metabolic markers related to exposure to ozone (0.4–1.2 ppm) for 4-h on gestation days 5 and 6 (window of implantation) in Long-Evans dams. To determine the effects of this exposure on trophoblast function, placental-derived, first trimester, HTR-8/SVneo cells were exposed to serum from air- or ozone (0.8 ppm×4 h)-exposed dams and examined for impacts on metabolic capacity, wound-closure, and invasion. Peri-implantation exposure to ozone induced ventilatory dysfunction and lung vascular leakage in pregnant rats, with little effect on most of the circulating markers measured. However, ozone inhalation induced a significant reduction in several serum cytokines (interferon-γ, interleukin-6, and interleukin-13). Treatment of HTR-8/SVneo trophoblasts with serum from ozone-exposed dams for 16-h downregulated metabolic capacity, wound-closure, and invasion through a Matrigel membrane compared with both air-serum and fetal bovine serum-treated cells. Ozone-serum treated cells increased the release of a critical inhibitor of invasion and angiogenesis (soluble fms-like receptor 1; sFlt1) compared with air-serum treatment. Together, our data suggest that circulating factors in the serum of pregnant rats exposed to ozone during implantation receptivity can hinder critical processes of implantation (eg, invasion and migration) and impair trophoblast metabolic capacity. [ABSTRACT FROM AUTHOR]

We have shown that acute ozone inhalation activates sympathetic-adrenal-medullary and hypothalamus-pituitary-adrenal stress axes, and adrenalectomy (AD) inhibits ozone-induced lung injury and inflammation. Therefore, we hypothesized that stress hormone receptor agonists (β2 adrenergic-β2AR and glucocorticoid-GR) will restore the ozone injury phenotype in AD, while exacerbating effects in sham-surgery (SH) rats. Male Wistar Kyoto rats that underwent SH or AD were treated with vehicles (saline + corn oil) or β2AR agonist clenbuterol (CLEN, 0.2 mg/kg, i.p.) + GR agonist dexamethasone (DEX, 2 mg/kg, s.c.) for 1 day and immediately prior to each day of exposure to filtered air or ozone (0.8 ppm, 4 h/day for 1 or 2 days). Ozone-induced increases in PenH and peak-expiratory flow were exacerbated in CLEN+DEX-treated SH and AD rats. CLEN+DEX affected breath waveform in all rats. Ozone exposure in vehicle-treated SH rats increased bronchoalveolar lavage fluid (BALF) protein, N -acetyl glucosaminidase activity (macrophage activation), neutrophils, and lung cytokine expression while reducing circulating lymphocyte subpopulations. AD reduced these ozone effects in vehicle-treated rats. At the doses used herein, CLEN+DEX treatment reversed the protection offered by AD and exacerbated most ozone-induced lung effects while diminishing circulating lymphocytes. CLEN+DEX in air-exposed SH rats also induced marked protein leakage and reduced circulating lymphocytes but did not increase BALF neutrophils. In conclusion, circulating stress hormones and their receptors mediate ozone-induced vascular leakage and inflammatory cell trafficking to the lung. Those receiving β2AR and GR agonists for chronic pulmonary diseases, or with increased circulating stress hormones due to psychosocial stresses, might have altered sensitivity to air pollution. [ABSTRACT FROM AUTHOR]

Problem: This study investigates the experience of depression from the perspective of Black single mothers, an understudied diverse-sub-group who consistently report high levels of depressive symptoms that go undetected and untreated. Participants: The sample consisted of 210 Black single mothers aged 18-45 who reside in urban communities. Methods: A descriptive, cross-sectional design was used to categorize the responses of Black single mothers to an open-ended question that asks about feelings of depression according to the four domains of the Centers for Epidemiologic Studies Depression Scale. Percentages and frequencies were used to describe the results of the analysis. Findings: The 303 usable responses were most consistent with the depressed affect domain (N = 172), followed by somatic activity (N = 108), interpersonal symptoms (N = 21), and lack of positive affect (N = 2). The most prevalent raw responses included sadness (N = 59), forms of anger (N = 48), depressed (N = 24), cry (N = 23), do not want to be around people (N = 21), lonely (N = 17), tired (N = 16), and stressed (N = 12). Conclusions/Implications: Consider culture and individualized assessments to explore feelings of anger and sadness when screening for depressive symptoms in specific sub-groups of Black single mothers. Consider the use of appropriate screening tools. [ABSTRACT FROM AUTHOR]

Halogenated platinum salts can trigger the development of occupational asthma. Until recently, laboratory research into the development and manifestation of platinum hypersensitivity responses were hindered by the lack of an animal model suitable for assessing the functional consequences of allergic sensitization. We employed a newly developed mouse model to assess the potential allergenicity of ammonium tetrachloroplatinate (ATCP), compare the relative potency of ATCP and another platinum salt, ammonium hexachloroplatinate (AHCP) and assess potential cross-reactivity. Mice were topically sensitized with ATCP before being challenged by intratracheal aspiration (IA) with ATCP. Ventilatory responses were assessed using whole-body plethysmography (WBP). An immediate response (IR) was observed in ATCP-sensitized and challenged mice. Two days later, responsiveness to the nonspecific stimuli methacholine (Mch) was detected in ATCP-sensitized mice using WBP. Bronchoalveolar lavage fluid collected from sensitized mice contained an average of 3.3% eosinophils compared to less than 0.5% in non-sensitized mice (p<.05). Serum harvested from sensitized mice also contained increased total serum immunoglobulin E (p<.05). These data are the first to demonstrate that topical exposure to ATCP is sufficient to develop immediate type hypersensitivity and that a single intra-airway challenge is capable of triggering pulmonary responses. To investigate potential cross-reactivity, mice were sensitized to AHCP and, challenged by a single IA with a second platinum compound, ATCP. Compared to non-sensitized mice challenged with ATCP, these mice exhibited an IR, responsiveness to Mch, and eosinophilic infiltration in the lungs similar to that achieved with AHCP challenge, thus demonstrating cross-reactivity. [ABSTRACT FROM AUTHOR]

Physical inactivity increases the prevalence of diseases. A significant decline is noted among female college students. This study identified factors that could be used to develop campus-wide physical activity (PA) initiatives to promote better health. Participants were diverse female students (N = 233, that completed an on-line PA survey. Logistic regression analysis with post-hoc pair-wise t-test comparisons revealed significant differences between racial/ethnic groups regarding moderate and vigorous PA. College represents a major transition period for young adults, and colleges and universities could promote more PA among female students, leading to better health well beyond graduation. [ABSTRACT FROM AUTHOR]

Physical activity is essential for overall good health and aids in the prevention and reduction of many diseases. In 2008, the U.S. Department of Health and Human Services (DHHS) issued the Physical Activity Guidelines for Americans to foster appropriate levels of physical activity at various ages of development. Despite these guidelines and the known benefit to being physically active; physical activity levels are significantly lower in Blacks, contributing to higher prevalence of poor health outcomes. Therefore, the purpose of this paper was to look at four national datasets [Youth Risk Behavior Survey (YRBS), Behavioral Risk Factor Surveillance System (BRFSS), The National Health and Nutrition Examination Survey (NHANES), and National Health Interview Survey (NHIS)] to identify any patterns and trends that could be used to improve physical activity behavior within this population. These national datasets were used to estimate the proportion of Black adults and youth meeting national physical activity recommendations overall--stratified by age, gender and other demographic characteristics, to help identify patterns. The proportion of Black youth reporting regular physical activity ranged from 33% to 52%; and of Black adults, 27% to 52%. Physical activity was highest among men, younger age groups, highest education and income groups, and those who were employed or married. Trends were consistent across surveys. Among Black youth, physical activity decline with increasing grade level, and improvements over the past 10 years have been minimal. The percentage of Black adults achieving physical activity guidelines has improved slightly over the last ten years, but physical activity participation is still low and continues to decline with age. Trends identified from examining these national datasets can be used to informdevelopment of physical activity interventions aimed at promoting and maintaining regular physical activity behavior among high risk subgroups across the life span. [ABSTRACT FROM AUTHOR]

Chronic diseases continue to be disproportionately higher in Black women in comparison with other ethnic groups, with physical inactivity being linked to the growing incidences of many of these diseases. The review of the literature indicates that attitude which is shaped by beliefs, self-efficacy, and cultural factors is a key variable in promoting physical activity (PA) in Black adolescent girls. Specific aims of this review were to identify PA interventions designed specifically for adolescent girls, with an emphasis on Black adolescent girls, and to identify what factor promotes PA in this group. The long-term goal is to use the information from this review to design effective PA programs aimed at Black adolescent girls. Physical activity and fitness were improved in four of the interventions in this review that focused on enhanced self-efficacy, goal setting, social support, and measures aimed at changing attitudes. Overall, this review shows that more effective interventions targeting Black adolescent girls are needed that consider the cultural factors (beliefs, self-efficacy, and family dynamics) that shape one’s attitude toward being physically active. [ABSTRACT FROM AUTHOR]

T-cell-dependent antibody responses (TDAR) are suppressed in female C57BL/6N mice exposed to ≥3.75 mg/kg of perfluorooctanoic acid (PFOA) for 15 days. To determine if suppression of humoral immunity by PFOA is peroxisome proliferator activated receptor alpha (PPARα)-dependent and if suppression is associated with specific targeting of T- or B-cells, three separate experiments were conducted: (1) female PPARαconstitutive knockout (PPARαKO; B6.129S4-Ppartm1GonzN12) and wild-type controls (WT; C57BL/6-Tac) exposed to 0, 7.5, or 30 mg PFOA/kg for 15 days were immunized on Day 11 with a T-cell-dependent antigen and sera then collected for measures of antigen-specific IgM titers (TDAR) 5 days later; (2) female C57BL/6N WT mice exposed to 0, 0.94, 1.88, 3.75, or 7.5 mg PFOA/kg for 15 days were immunized with a T-cell-independent antigen on Day 11 and sera were then collected for analyses of antigen-specific IgM titers (TIAR) 7 days later; and (3) splenic lymphocyte phenotypes were assessed in unimmunized female C57BL/6N WT mice exposed to 0, 3.75, or 7.5 mg PFOA/kg for 10 days to investigate effects of PFOA in the absence of specific immunization. Separate groups of mice were immunized with a T-cell-dependent antigen after 11 days of exposure and splenic lymphocyte sub-populations were assessed after 13 or 15 days of exposure to assess numbers of stimulated cells. The results indicated that exposure to ≥1.88 mg PFOA/kg suppressed the TIAR; exposure to 30 mg PFOA/kg suppressed the TDAR in both PPARαKO and WT mice. The percentage of splenic B-cells was unchanged. Results obtained in the PPARαKO mice indicated that PPARαsuppression of TDAR was independent of PPARαinvolvement. Suppression of the TIAR and the TDAR with minimal lymphocyte sub-population effects suggested that effects on humoral immunity are likely mediated by disruption of B-cell/plasma cell function. [ABSTRACT FROM PUBLISHER]

The article focuses on the decline of physical activity among African American adolescent girls in high school due to factors inclwuding physical appearances, scheduling of physical education (PE) classes, and poor maintenance of shower facilities.

The article discusses the study that explored the perspectives of African-American mothers of adolescent girls regarding physical activity, for the identification of solutions for the improvement or facilitation of physical activity among their daughters. Findings discussed include emergence of themes such as knowledge and importance of keeping physical activity fun, emergence of need for time-management strategies as a significant factor, and mothers need help to integrate physical activity.

Community members have identified second-hand smoke exposure among young women and children within First Nations communities as a concern. As part of a community-based research project, we analyzed experiences related to establishing smoke-free public spaces and the challenges related to smoking and bingo. The purpose of this study was to a) describe and compare community smoking at bingo in First Nations communities, and b) draw implications for assessing and supporting community readiness for comprehensive tobacco control policies (TCPs). Data were collected using individual interviews, group discussions, and observations in the community. The establishment of smoke-free public spaces in communities evolved out of concern by people traditionally responsible for the well-being of the community. Despite close proximity and similar socioeconomic contexts, readiness to extend these successes to bingos held in community halls was influenced by three main factors: a) economic drivers, b) the smoking majority, and c) grassroots support. Although models for assessing community readiness provide a useful starting point for understanding local TCP development and implementation in First Nations communities, other factors also need to be considered. Using a comprehensive approach to assessing community readiness has the potential to increase success in extending TCPs and practices in First Nations communities in ways that are culturally relevant, address local conditions, and build on existing efforts. [ABSTRACT FROM AUTHOR]

Many potential applications in nanotechnology envisage the use of better-dispersed and functionalized preparations of carbon nanotubes. Single-walled carbon nanotubes (SWCNTs) were treated with 1:1 mixtures of concentrated nitric and sulfuric acids for 3 min in a microwave oven under 20 psi pressure followed by extensive dialysis to remove the acids. This treatment resulted in acid functionalized SWCNTs (AF-SWCNTs) that had high negative charge (Zeta potential -40 to -60 mV) and were well dispersed (98% of the particles <150 nm) in aqueous suspensions. In vitro and in vivo toxic effects of SWCNTs and AF-SWCNTs were compared. AF-SWCNTs exerted a strong cytotoxic effect on LA4 mouse lung epithelial cells in culture that could be blocked by prior treatment of the nanotubes with poly L-lysine which neutralized the electric charge and promoted re-agglomeration. AF-SWCNT, but not the unmodified SWCNT preparations, strongly inhibited cell cycling of LA4 cells. Both SWCNTs and AF-SWCNTS were however equally effective in inducing apoptotic responses in LA4 cells as examined using an Annexin V binding assay. Oro-pharyngeal aspiration of AF-SWCNT preparation induced a strong acute inflammatory response in the lungs of CD1 mice, compared to control SWCNTs which caused only a marginal effect. Taken together the results indicate that unlike pristine SWCNTs, acid-functionalized SWCNT preparations exert strong toxic effects in vitro and in vivo and these effects can be reversed by neutralizing their surface charge. [ABSTRACT FROM AUTHOR]

To delineate the differences between the structural requirements necessary for recognition at sigma-1 and sigma-2 receptors, a range of phenethyl- and phenylpropylpiperidines were evaluated in binding assays. Phenethylpiperidines were found to favor sigma-1 receptors, whereas phenylpropylpiperidines tend to favor sigma-2 receptors. It appears that phenylpropylamine is a potential pharmacophore for selective sigma-2 ligands. [Copyright &y& Elsevier]

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant that produces adverse effects on the immune system of experimental animals. In this study, the effect that TCDD has on the antibody plaque-forming cell (PFC) response to the T cell-independent (TI) antigen trinitrophenyl-lipopolysaccharide (TNP-LPS) was compared in adult female B6C3F1 mice and F344 rats. Mice or rats were given a single intraperitoneal injection of TCDD at doses ranging from 1 to 30 μg/kg, 7 days prior to immunization with TNP-LPS by intravenous injection. Three days later body, spleen, thymus, and liver weights were measured and the PFC response to TNP-LPS was determined. Thymus weights were decreased at 10 and 30 μg TCDD/kg, whereas spleen weights were decreased and liver weights increased in mice dosed at 3,10, and 30 μg/kg. Mice dosed at 10 and 30 μg TCDD/kg had suppressed PFC responses and serum hemagglutination liters. In rats, thymus weights were decreased and liver weights increased at 3, 10, and 30 μg TCDD/kg; however, the PFC response and serum hemagglutination titers to TNP-LPS were suppressed only at 30 μg/kg TCDD. TCDD did not affect splenic lymphocyte subsets evaluated by flow cytometry. These results indicate that TCDD suppresses the TI antibody response to TNP-LPS in both B6C3F1 mice and F344 rats, with mice more sensitive to suppression by TCDD than rats. [ABSTRACT FROM AUTHOR]

2-Methoxyethanol (ME) is metabolized to 2-methoxyacetic acid (MAA) via the intermediate metabolite methoxyacetaldehyde (MAAD). Both ME and MAA have been shown in this laboratory to be immunosuppressive in rats following oral dosing. In this study, the plaque-forming cell (PFC) response to trinitrophenyl-lipopolysaccharide (TNP-LPS) was used to determine if MAAD is immunosuppressive in rats. Rats pretreated with the aldehyde dehydrogenase inhibitors disulfiram (2 mmol/kg) or cyanamide (0.48 mmol/kg) followed by oral dosing with ME (2.64 mmol/kg) resulted in suppressed PFC responses equivalent to the suppressed responses of rats dosed with ME alone. Rats pretreated with disulfiram and then dosed with 2.64 mmol/kg 2-methoxyethyl acetate (MEA), also resulted in suppressed PFC responses similar to that of MEA alone. In contrast, coadministration of the alcohol dehydrogenase inhibitor 4-methylpyrazole (1.2 mmol/kg) with ME or MEA blocked suppression of the PFC response following exposure to ME or MEA alone. Oral dosing with equimolar (2.64 mmol/kg) concentrations of ME, MAA, or MAAD resulted in equivalent suppression of the TNP-LPS PFC response. Rats exposed to either disulfiram or cyanamide and MAAD also resulted in suppression of the PFC response. These results indicate that metabolism of ME to either MAAD or MAA is required for immunosuppression, and that these two metabolites are equipotent immunosuppressants in the rat. [ABSTRACT FROM PUBLISHER]

Oral dosing of adult male F344 rats with the glycol ether 2-methoxyethanol (ME) or its principal metabolite 2-methoxyacetic acid (MAA) results in the suppression of the primary plaque-forming cell (PFC) response to trinitrophenyl-lipopolysaccharide (TNP-LPS). In the present study, the PFC response to TNP-LPS was used to evaluate the immunotoxic potential of ethylene glycol (EG) as well as the glycol ethers 2-methoxyethyl acetate (MEA), 2-(2-methoxyethoxy) ethanol, bis(2-meth- oxyethyl) ether, 2-ethoxyethanol and its principal metabolite 2-ethoxyacetic acid, 2-ethoxyethyl acetate, and 2-butoxyethanol relative to ME and MAA. Rats were immunized with TNP-LPS and then exposed 4 and 28 hr later to 50, 100, 200, or 400 mg/kg of glycol ether or EG. Three days following immunization, the PFC response to TNP-LPS was determined. In addition to ME and MAA, only MEA, which was as effective as ME, suppressed the PFC response to TNP-LPS. Concomitant administration of the alcohol dehydrogenase inhibitor 4-methylpyrazole with ME or MEA prevented suppression of the PFC response by these glycol ethers. These results indicate that of the chemicals tested only ME, MEA, and MAA are immunosup pressive, and that oxidative metabolism via alcohol dehydrogenase is necessary for ME- and MEA-suppression of the response to TNP-LPS. [ABSTRACT FROM PUBLISHER]

The quantification of rat splenic lymphocyte populations using immunofluorescent staining and flow cytometry was evaluated in an interlaboratory study involving 6 independent facilities employing a common protocol. The study had three specific aims: (1) to establish baseline values for rat splenic lymphocyte populations, (2) to examine variability in flow cytometry data both within and am ong laboratories, and (3) to evaluate single versus dual cell labeling of T-cell subpopulations, as well as quadrant and histogram analysis procedures. Splenic lymphocytes were enumerated following the lysis of red blood cells (RBC) with ammonium chloride. B-cells (anti-rat kappa light chain; clone OX12) were exam ined using a single im munofluorescent label, whereas T-cells (anti-CD5; OX19), T (T ) (anti-CD4; W3/ 25), and T (T ) helper h cytotoxic/ su ppressor cyt/ su p (anti-CD8; OX8) cells were examined using both single and dual labeling. Cell recoveries and viabilities reported by each laboratory following the lysis of RBC ranged from 27 to 87% and 82 to 95%, respectively. Splenic differential counts indicated that approximately 20% of rat splenocytes are not lymphocytes. For quantitating relative and absolute num bers of lymphocytes, intralaboratory variability was sim ilar across analysis and labeling procedures. Intralaboratory variability was higher and interlaboratory reference ranges larger when absolute versus relative numbers of lymphocytes were compared. Statistical performance indices indicated that no analysis or labeling method was consistently performed among the laboratories. Since monoclonal antibodies for labeling rat T and T cells recognize cross-reacting epitopes on other h cyt/ su p cell populations, the authors recomm end dual labeling of T-cell subpopulations and quadrant analysis procedures. The following are the overall mean relative (%) and absolute numbers, respectively, for each of the various splenic lymphocyte populations obtained in this study using dual labeling of T and T cells h cyt/ sup and quadrant analysis: 20 - 1 (2.2- 0.2 2 108) W3/ 25+OX19+ cells; 17 - 2 (1.8 - 0.3 2 108) OX8+OX19+ cells; 43 - 2 (4.7- 0.5 2 108) OX19+ cells; and 39 - 2 (4.3- 0.5 2 108) OX12+ cells. This study indicates that additional standardization of sample preparation and analysis procedures (i.e., RBC lysis and cell gating) may be needed in the use of flow cytometry in imm unotoxicology studies. [ABSTRACT FROM AUTHOR]

Black/African American women are at high risk for depression, yet are underrepresented in psychiatric genetic research for depression prevention and treatment. Little is known about the factors that influence participation in genetic testing for Black/African American women at risk. The purpose of this study was to elicit the beliefs that underlie participation in genetic testing for depression in Black/African American mothers, a subgroup at high risk. Willingness to participate in genetic testing procedures was also determined. A qualitative, descriptive design was employed. Exactly 19 mothers aged 21–42 completed open-ended questionnaires. Directed content and descriptive analyses of the text were conducted based on the Theory of Planned Behavior. Salient beliefs included: behavioral advantages—diagnosing/detecting depression (31.6%), finding cure/treatment (21.1%); disadvantages—not finding follow-up treatment/help (21.1%); salient referents, who approves—family members (47.4%), agencies/organizations (26.3%); who disapproves—church associates (21.1%). Control beliefs included: barriers—unpleasant/difficult testing procedures (42.1%), limited knowledge about the purpose of testing (26.3%); facilitator—a convenient location (21.1%). Most mothers (89.5%) indicated willingness to participate in testing. Interventions can target families, address barriers, emphasize future benefits, and use convenient locations and community-based participatory research methods. Policies can address social determinants of participation to increase inclusion of these mothers in psychiatric genetic research. [ABSTRACT FROM AUTHOR]