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At least 199 records · Page 11Linked to original sources

Exposure to multiple doses of UVB radiation reduces the numbers of epidermal Langerhans cells and lymph node dendritic cells in mice.

Immune suppression following UVB irradiation is partly attributed to the effects of the exposure on antigen-presenting cells. Following a single UVB irradiation, there is a decrease in epidermal Langerhans cell numbers; this is accompanied by an increase in the number of dendritic cells (DC) in lymph nodes draining the irradiated site. We investigated whether a similar effect occurred following multiple UVB exposures. Mice were irradiated on their ears and shaved dorsal skin twice a week for 3 weeks. After the final exposure, the number of ATPase(+) Langerhans cells in epidermal sheets prepared from the ears was found to be decreased by 33% compared to unirradiated controls. The number of DC in the draining lymph nodes (DLN) did not increase as might have been expected; rather, a significant decrease of approximately 30% in DC numbers in the DLN of UVB-irradiated mice compared with unirradiated controls occurred. This decrease in antigen-presenting cells in both the epidermis and the DLN may be an important contributing factor to the immune suppression that follows multiple UVB exposures.

Animals↗

Estimation of the joint risk for multiple-compound exposure based on single-compound experiments.

In the absence of data from multiple-compound exposure experiments, the health risk from exposure to a mixture of chemical carcinogens is generally based on the results of the individual single-compound experiments. A procedure to obtain an upper confidence limit on the total risk is proposed under the assumption that total risk for the mixture is additive. It is shown that the current practice of simply summing the individual upper-confidence-limit risk estimates as the upper-confidence-limit estimate on the total excess risk of the mixture may overestimate the true upper bound. In general, if the individual upper-confidence-limit risk estimates are on the same order of magnitude, the proposed method gives a smaller upper-confidence-limit risk estimate than the estimate based on summing the individual upper-confidence-limit estimates; the difference increases as the number of carcinogenic components increases.

Animals↗

[Changes in the morphological structure of the skin and internal organs of guinea pigs after multiple epicutaneous exposures to furfural, a distillate of D-11 mineral oil and their combinations].

Experimental multiple epicutaneous exposure of guinea pigs to furfural and D-11 mineral oil distillate and their combinations in various concentrations has resulted in structural changes of the skin and viscera. These changes were dose-dependent. Combined exposure to both agents resulted in more grave disorders than isolated exposures in the same doses.

Administration, Cutaneous↗

Standardized test performance of children with a history of prenatal exposure to multiple drugs/cocaine.

Twenty-four children, age 14 to 50 months, with a history of prenatal exposure to multiple drugs including cocaine, were matched by adjusted birth age and sex to 24 children with no history of drug exposure. All children had been living in stable, drug-free environments from at least the age of 11 months. Tests administered included the Sequenced Inventory of Communicative Development-Revised (SICD), the Bayley Scales of Infant Development, and the Peabody Picture Vocabulary Test-Revised (PPVT-R). Results indicated significant differences between groups and genders on the SICD when age was covaried and between groups on the Bayley. No groups or genders differed on the PPVT-R. Many (45.8%) of the children in the drug-exposed group qualified for intervention services according to Washington state criteria. Subject characteristics, other than age, did not play a significant role in the findings of group differences. It is concluded that, due to the cumulative effects of prenatal history, these children should be considered at risk for language delay.

Child, Preschool↗

Effects of sequential exposure to multiple concentrations of methylmercury in the rat hippocampal slice.

Two experiments explored the effects of sequential exposure to multiple concentrations of methylmercury (MeHg) on rat hippocampal slice synaptic transmission and excitability in area CA1. When hippocampal slices were exposed to 0.1, 1, 10, and 100 microM MeHg chloride in successive 30-min exposures, MeHg produced an increase in excitability over baseline levels throughout the 1 microM exposure and the first 5 min of the 10 microM exposure, followed by profound suppression of excitability at the 100 microM level. When hippocampal slices were exposed to 10, 25, 50, 75, and 100 microM concentrations, MeHg produced an increase in excitability throughout most of the 10 and 25 microM exposures, followed by profound suppression of excitability at the 50 microM level of exposure. In both series of concentrations, MeHg suppressed local inhibitory systems prior to suppressing excitatory systems. In a third experiment, a single exposure of 50 microM MeHg suppressed both presynaptic and postsynaptic responses recorded in stratum radiatum with the same time course, suggesting that the observed suppressive effects of MeHg were not primarily synaptic.

Animals↗

Using biologic markers in blood to assess exposure to multiple environmental chemicals for inner-city children 3-6 years of age.

We assessed concurrent exposure to a mixture of > 50 environmental chemicals by measuring the chemicals or their metabolites in the blood of 43 ethnically diverse children (3-6 years of age) from a socioeconomically disadvantaged neighborhood in Minneapolis. Over a 2-year period, additional samples were collected every 6-12 months from as many children as possible. We analyzed blood samples for 11 volatile organic compounds (VOCs), 2 heavy metals (lead and mercury, 11 organochlorine (OC) pesticides or related compounds, and 30 polychlorinated biphenyl (PCB) congeners. The evidence suggests that numerous VOCs originated from common sources, as did many PCBs. Longitudinal measurements indicate that between-child variance was greater than within-child variance for two VOCs (benzene, toluene), for both heavy metals (Pb, Hg), for all detectable OC pesticides, and for 15 of the measured PCB congeners (74, 99, 101, 118, 138-158, 146, 153, 156, 170, 178, 180, 187, 189, 194, 195). Despite the relatively small sample size, highest measured blood levels of 1,4-dichlorobenzene, styrene, m-/p-xylene, Pb, Hg, heptachlor epoxide, oxychlordane, dichlorodiphenyldichloroethene (p,p -DDE), trans-nonachlor, and PCB congeners 74, 99, 105, 118, 138, 146, 153, 156, 170, and 180 were comparable with or higher than 95th percentile measurements of older children and adults from national surveys. Results demonstrate that cumulative exposures to multiple environmental carcinogens and neurotoxins can be comparatively high for children from a poor inner-city neighborhood.

Biomarkers↗

Modulation of biochemical and cytological profile of bronchoalveolar lavage constituents in rats following split-dose multiple inhalation exposure to methyl isocyanate.

1. Studies were carried out to explore the acute pulmonary effects of equal, split-dose, multiple inhalation exposures of rats to methyl isocyanate (MIC), (0.32 mg l-1, 8 min x 10 exposures) as reflected by alterations in bronchoalveolar lavage fluid (BALF) constituents and to evaluate recovery, if any, following survival in a MIC-free environment, 10 d after the last MIC exposure. 2. In the BALF of MIC-exposed rats, there was an increase in the total number of cells and the number of cells showing enhanced dye uptake and reduction of nitroblue tetrazolium chloride. The cell-free BALF showed increases in total protein, sialic acids and lactic acid contents and lactate dehydrogenase activity. 3. In rats exposed to MIC and sacrificed 10 d after survival in a MIC-free environment, there was a reduction in the cellular and biochemical constituents of BALF. The phagocytic potential of macrophages was, however, also decreased under this regime.

Administration, Inhalation↗

Comparison of the disposition of butadiene epoxides in Sprague-Dawley rats and B6C3F1 mice following a single and repeated exposures to 1,3-butadiene via inhalation.

1,3-Butadiene (BD), a compound used extensively in the rubber industry, is a potent carcinogen in mice and a weak carcinogen in rats in chronic carcinogenicity bioassays. While many chemicals are known to alter their own metabolism after repeated exposures, the effect of exposure prior to BD on its in vivo metabolism has not been reported. The purpose of the present research was to examine the effect of repeated exposure to BD on tissue concentrations of two mutagenic BD metabolites, butadiene monoepoxide (BDO) and butadiene diepoxide (BDO2). Concentrations of BD epoxides were compared in several tissues of rats and mice following a single exposure or ten repeated exposures to a target concentration of 62.5 ppm BD. Female Sprague-Dawley rats and female B6C3F1 mice were exposed to BD for 6 h or 6 h x 10 days. BDO and BDO2 were quantified in blood and several other tissues following preparation by cryogenic vacuum distillation and analysis by multidimensional gas chromatography-mass spectrometry. Blood and lung BDO concentrations did not differ significantly (P < or = 0.05) between the two exposure regimens in either species. Following multiple exposures to BD, BDO levels were 5- and 1.6-fold higher (P < or = 0.05) in mammary tissue and 2- and 1.4-fold higher in fat tissue of rats and mice, respectively, as compared with single exposures. BDO2 levels also increased in rat fat tissue following multiple exposures to BD. However, in mice, levels of this metabolite decreased by 15% in fat, by 28% in mammary tissue and by 34% in lung tissue following repeated exposures to BD. The finding that the mutagenic epoxide BDO, which is the precursor to the highly mutagenic BDO2, accumulates in rodent fat may be important in assessing the potential risk to humans from inhalation of BD.

Adipose Tissue↗

A meta-analysis of occupational trichloroethylene exposure and multiple myeloma or leukaemia.

BACKGROUND: Trichloroethylene (TCE) has been widely used as an industrial solvent and degreasing agent. AIMS: We conducted a meta-analysis of epidemiologic studies of occupational TCE exposure and multiple myeloma (MM) or leukaemia. METHODS: We identified a total of eight cohort or case-control studies that enumerated a TCE-exposed study population and presented relative risk (RR) estimates for MM (n = 7) and/or leukaemia (n = 7). The individual studies included aerospace or aircraft workers (n = 3 studies), workers from a transformer manufacturing plant (n = 1 study) and workers from numerous occupations who, based on biomonitoring or extensive industrial hygiene exposure measurements, were likely exposed to TCE (n = 4). We used random effects models to calculate summary relative risk estimates (SRRE). In addition, we examined heterogeneity across studies and the relative influence of each individual study on the overall meta-analysis. RESULTS: No association was observed for MM (SRRE = 1.05, 95% CI: 0.80-1.38; P value for heterogeneity = 0.94) or leukaemia (SRRE = 1.11, 95% CI: 0.93-1.32; P value for heterogeneity = 0.50), based on TCE-exposed subgroup meta-analyses. Study-specific RR estimates for MM ranged between 0.57 and 1.62. RRs for leukaemia ranged between 1.05 and 1.15 in five studies, while one study reported a 2-fold increased RR and another study reported an inverse association of 0.60. All confidence intervals (CIs) for study-specific estimates included 1.0. CONCLUSIONS: The results of this meta-analysis do not support an etiologic association between occupational TCE exposure and risk of MM or leukaemia.

Aerospace Medicine↗

Prenatal alcohol exposure assessment: multiple embedded measures in a prenatal questionnaire.

Alcohol exposure during pregnancy is a well-recognized public health problem. Accurate assessment of prenatal alcohol exposure is especially important to identify women in need of intervention. In this study, a 36-item prenatal questionnaire was utilized to survey a representative sample of prenatal care providers to examine prevalence rates of exposure. The questionnaire included three common screening tools for alcohol use during pregnancy and the items necessary to establish a maternal risk profile. In North Dakota, 1081 pregnant women were included in the sample. Eighty (7.4%) were Native American and 952 (88%) were White. The TWEAK screening tool was positive for 253 (23.4%) of the women. Native American women had a 71% increase in positive TWEAK screenings compared to White women. Logistic regression was used to develop a high-risk model. The data from prenatal care can also be used for maternal risk stratification. Early identification can provide opportunity for early interventions to decrease total exposure during pregnancy and to improve the outcome for the child.

Adolescent↗

Relationship between exposure to multiple noise sources and noise annoyance.

Relationships between exposure to noise [metric: day-night level (DNL) or day-evening-night level (DENL)] from a single source (aircraft, road traffic, or railways) and annoyance based on a large international dataset have been published earlier. Also for stationary sources relationships have been assessed. Here the annoyance equivalents model concerning noise annoyance from combined sources and the underlying assumptions are presented. The model first translates the noise from the individual sources into the equally annoying sound levels of a reference source, road traffic, and then sums these levels giving total level L. The annoyance from the combined sources is found by substituting exposure L in the road traffic exposure-annoyance relationship. The most important assumption, independence of the contributions of the sources, is discussed. It appears that independence will be violated substantially only due to the effect of the presence or absence of a quiet side of building which is not incorporated in the model. For use in practice the application of the model is broken down in five steps. The step by step procedure can be used for the assessment of the total noise level and the associated total annoyance on the basis of the DNL or DENL values of the individual sources.

Acoustics↗

[A case of pulmonary hyalinizing granuloma with its occupational history of dust exposure].

Multiple pulmonary nodules were found in a patient who had an occupational history of coal mining for eleven years and road construction for fifteen years. An open lung biopsy was performed, because nodules had increased in size compared to previous ones and a trasbronchial biopsy was not diagnostic. The nodules were composed of dense concentric lamellar collagenous structures with a serpentine pattern surrounded by an infiltration of histiocytes, lymphocytes and plasma cells with Russel bodies. These findings are compatible with pulmonary hyalinizing granuloma (PHG) named by Liebow A. A. The etiopathogenetic mechanism and the difference between PHG and silicotic nodule is discussed.

Aged↗

Halothane-induced hepatic microsomal lipid peroxidation in guinea pigs and rats.

Halothane-induced hepatic microsomal lipid peroxidation in guinea pigs and rats was examined with respect to the mixed function oxidase system, anaerobic dehalogenation activity of halothane, and the antioxidant system. The levels of cytochrome P-450 and NADPH-cytochrome P-450 reductase were significantly higher in guinea pigs than in rats. There was no difference between the two animals in anaerobic dehalogenation activity of halothane per cytochrome P-450 in microsomes. Microsomal alpha-tocopherol was significantly lower in guinea pigs than in rats, and was increased by multiple exposure to halothane in guinea pigs but remained lower than in rats. Microsomal alpha-tocopherol was decreased in rats by multiple exposure. The concentration of reduced glutathione and ascorbic acid was decreased significantly by multiple exposure to halothane in guinea pigs but not in rats. These results suggest that the higher level of halothane-induced hepatic microsomal lipid peroxidation in guinea pigs is due to the large production of radical metabolites resulting from the large amounts of cytochrome P-450, the high activity of NADPH-cytochrome P-450 reductase, and the low concentration of microsomal alpha-tocopherol.

Animals↗

Multiple channel exposure therapy: combining cognitive-behavioral therapies for the treatment of posttraumatic stress disorder with panic attacks.

A large proportion of patients who present for treatment of posttraumatic stress disorder (PTSD) experience comorbid panic attacks, yet it is unclear to what extent currently available PTSD treatment programs address this problem. Here we describe a newly developed treatment, multiple-channel exposure therapy (M-CET), for comorbid PTSD and panic attacks. The treatment utilizes elements of cognitive processing therapy treatment for PTSD and elements of panic control treatment to target physiological, cognitive, and behavioral symptoms. Preliminary results suggest that M-CET may provide a promising treatment program for a subset of patients with PTSD who experience panic attacks. In addition, guidelines for conducting M-CET with clients who have been exposed to diverse traumatic events are provided.

Cognitive Behavioral Therapy↗

Neoplastic transformation of primary tracheal epithelial cell cultures.

Primary cultures of rat tracheal epithelial cells were treated with the chemical carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) to quantitatively study the early events during neoplastic transformation. Epithelial cells were dissociated from tracheas of specific-pathogen-free Fischer-344 rats and were plated on collagen-coated tissue culture dishes. To determine cytotoxicity, cells were exposed on day 1 to various concentrations of MNNG for 3 h and colony forming efficiency (CFE) was determined on day 7. MNNG at a concentration of 0.1 microgram/ml did not decrease CFE as compared to the control cultures, whereas 1 microgram/ml reduced the CEF by 75%. For transformation studies, primary cell cultures received single exposures to MNNG (0.1-0.6 microgram/ml) or multiple exposures to 0.1 microgram/ml of MNNG for 3 h between days 1 and 17. In carcinogen-exposed cultures, morphologically altered foci appeared on day 18, recognizable by high cell density. Transformation frequencies between 1 and 8% were observed depending on MNNG concentration. Cultures containing altered foci continued to grow during the third and fourth week when control cultures had ceased to proliferate and exfoliated from the dish. Over 40% of the cultures which received multiple exposures to MNNG acquired cell line status and could be subcultured greater than or equal to 20 times. None of the 30 control cultures became cell lines. Seventy per cent of MNNG-exposed cell lines showed the anchorage independent growth phenotype at passage 20 as judged by growth in agarose. Four of 10 cultures exposed either 6 or 8 times to MNNG formed invasive squamous cell carcinomas at passage 20 upon inoculation into nude mice. Based on these and previous studies, we feel that unrestricted cell replication is an early key event in carcinogen-exposed epithelial cell populations, preceding neoplastic transformation.

Animals↗

Single and multiple desipramine exposures of cultured cells. Changes in cellular anisotropy and in lipid composition of whole cells and of plasma membranes.

Effects of the antidepressant drug desipramine (DMI) on fluorescence anisotropy were studied in living cultured human fibroblasts, rat brain astrocytes and rat ROC-1 hybridoma cells (oligodendrocytes x C6). Fluorescence anisotropy, a measure for fluidity, was measured by means of a fluorescence polarization technique using a set of n-(9-anthroyloxy) fatty acids as markers. Apparent fluorescence anisotropies were determined in cells following single or multiple dose exposures to 5 microM DMI at 37 degrees and compared to control cells. In all three cell types single doses of DMI led to significant decreases in anisotropies of the deeper layers (12-AS) of the membranes only, suggesting increases in fluidity. Repeated exposures to 5 microM DMI led to cell specific, significant changes in anisotropies of the superficial membrane layers, as determined by 2-AP, 6-, 7- and 9-AS. The resulting anisotropy values of the three different cell types became more alike than prior to DMI exposure. Alterations in anisotropies were accompanied with changes in the phospholipid patterns of whole cells and isolated plasma membrane vesicles. The changes of PC/PE ratios were consistent with changes observed in fluorescence anisotropies. Such alterations may be individual regulatory responses of the cells to the chronic presence of the drug within the membranes.

Animals↗

An aggregate public health indicator to represent the impact of multiple environmental exposures.

We present a framework to aggregate divergent health impacts associated with different types of environmental exposures, such as air pollution, residential noise, and large technologic risks. From the policy maker's point of view, there are at least three good reasons for this type of aggregation: comparative risk evaluation (for example, setting priorities), evaluation of the efficiency of environmental policies in terms of health gain, and characterizing health risk associated with geographical accumulation of multiple environmental exposures. The proposed impact measure integrates three important dimensions of public health: life expectancy, quality of life, and number of people affected. Time is the unit of measurement. "Healthy life years" are either lost by premature death or by loss of quality of life, measured as discounted life years within a population. Severity weights (0 for perfect health, 1 for death) are assigned to discount the time spent with conditions associated with environmental exposures. We combined information on population exposure distribution, exposure response relations, incidence, and prevalence rates to estimate annual numbers of people affected and the duration of the condition, including premature death. Using data from the fourth Dutch National Environmental Outlook, we estimated that the long-term effects of particulate air pollution account for almost 60% of the total environment-related health loss in the Netherlands as modeled here. Environmental noise accounts for 24%, indoor air pollution (environmental tobacco smoke, radon, and dampness, as well as lead in drinking water) for around 6%, and food poisoning (or infection) for more than 3%. The contribution of this set of environmental exposures to the total annual burden of disease in the Netherlands is less than 5%.

Cost of Illness↗