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PubMedDate not supplied

Prevention of ultraviolet-B radiation damage by resveratrol in mouse skin is mediated via modulation in survivin.

Nonmelanoma skin cancer is the most frequently diagnosed malignancy in the United States, and multiple exposures to solar ultraviolet (UV) radiation (particularly its UV-B component, 290-320 nm), is its major cause. 'Chemoprevention' by naturally occurring agents is being appreciated as a newer dimension in the management of neoplasia including skin cancer. We recently demonstrated that resveratrol (trans-3, 5, 4-trihydroxystilbene), an antioxidant found in grapes, red wines and a variety of nuts and berries, imparts protection from acute UV-B-mediated cutaneous damages in SKH-1 hairless mice. Understanding the mechanism of resveratrol-mediated protection of UV responses is important. We earlier demonstrated that resveratrol imparts chemopreventive effects against multiple UV-exposure-mediated modulations in (1) cki-cyclin-cdk network, and (2) mitogen activated protein kinase (MAPK)-pathway. This study was conducted to assess the involvement of inhibitor of apoptosis protein family Survivin during resveratrol-mediated protection from multiple exposures of UV-B (180 mJ/cm(2); on alternate days; for a total of seven exposures) radiations in the SKH-1 hairless mouse skin. Our data demonstrated that topical pre-treatment of resveratrol (10 micromol in 200 microl acetone/mouse) resulted in significant inhibition of UV-B exposure-mediated increases in (1) cellular proliferations (Ki-67 immunostaining), (2) protein levels of epidermal cyclooxygenase-2 and ornithine decarboxylase, established markers of tumor promotion, (3) protein and messenger RNA levels of Survivin, and (4) phosphorylation of survivin in the skin of SKH-1 hairless mouse. Resveratrol pretreatment also resulted in (1) reversal of UV-B-mediated decrease of Smac/DIABLO, and (2) enhancement of UV-B-mediated induction of apoptosis, in mouse skin. Taken together, our study suggested that resveratrol imparts chemopreventive effects against UV-B exposure-mediated damages in SKH-1 hairless mouse skin via inhibiting Survivin and the associated events.

Animals↗
PubMed1997

Multiple myeloma and benzene exposure in a multinational cohort of more than 250,000 petroleum workers.

Case reports have suggested an association between benzene exposure and multiple myeloma. Because petroleum workers are exposed to benzene or benzene-containing liquids, studies of these workers provide an opportunity for investigating the relationship between benzene and multiple myeloma. A large number of cohort studies of petroleum workers have been conducted. However, few of them have reported results of multiple myeloma separately. One reason is that multiple myeloma is usually grouped with other lymphopoietic cancers in the analysis. Another reason is that multiple myeloma is relatively rare, and few individual studies are large enough to provide reliable risk estimates. To determine the risk of multiple myeloma in petroleum (refinery, distribution, production, and pipeline) workers, we have identified 22 cohort mortality studies of petroleum workers in the United States, the United Kingdom, Canada, and Australia. Authors of these studies were contacted, and data on the number of observed deaths and age-specific person-years of observation were requested. Data from individual studies were combined in a pooled analysis (meta-analysis). In addition to the pooled analyses, results for individual cohorts, most of which have never been reported before, are also presented. The combined multinational cohort consisted of more than 250,000 petroleum workers, and the observation period covered an interval of 55 years from 1937 to 1991. A total of 205 deaths from multiple myeloma were observed, compared to 220.93 expected, a total derived from respective national mortality rates. The corresponding standardized mortality ratio (SMR) was 0.93 and the 95% confidence interval (95% CI) was 0.81-1.07. Additional analyses were performed by type of facility and industrial process. Stratum-specific SMRs (95% CIs) were 0.92 (0.77-1.09) for refinery workers and 0.93 (0.69-1.23) for distribution workers. When individual cohorts were stratified by length of observation, no pattern was detected. The pooled analysis indicates that petroleum workers are not at an increased risk of multiple myeloma as a result of their exposure to benzene, benzene-containing liquids, or other petroleum products in their work environment. This conclusion is supported by cohort studies of workers in other industries who were exposed to benzene as well as by population-based case-control studies of multiple myeloma and occupational exposures.

Australia↗
PubMed1992

Hematological parameters are altered during cold air exposure.

Whole blood hematocrit (HCT) decreases during multiple exposures to cold air. To better understand this finding, we have analyzed hematological profiles in 27 normal adult men exposed repeatedly to cold air in one of two experimental protocols. Experiment I was a cold air acclimatization study (CAA) conducted with two groups of 8 men in each group before, during, and after 80 separate 30-minute cold (4 degrees C) air exposures. As part of a metabolic study, half of the men received placebo daily (n = 8), and the other half received an oral daily maintenance dose of the thyroid hormone triiodothyronine (T3) (30 micrograms/day). Blood was analyzed prior to and after every 20 cold exposures. Both groups reacted similarly. When compared with basal conditions, hematocrit (HCT) and erythrocyte counts (RBC) were decreased (p less than 0.05); mean corpuscular hemoglobin concentration (MCHC) and plasma volume (PV) were increased with cold exposure (p less than 0.05). Hemoglobin (Hb), leukocyte counts (WBC), and mean corpuscular volume (MCV) were unchanged. Experiment II was carried out with 9 military volunteers during extended arctic winter field operations (EAO) in Utah and Alaska. Blood was analyzed prior to and after completion of EAO. A changing hematological profile similar to that in the CAA protocol was found. Hematocrit and RBC were decreased (p less than 0.02); MCHC and PV were increased (p less than 0.02). Hemoglobin, WBC, and MCV were unchanged. In addition, there was a negative correlation between HCT and the absolute reticulocyte count in this second experiment. It would appear that in instances of cold stress, whether induced or naturally occurring, certain blood cellular elements respond in a similar adaptive manner.

Acclimatization↗
PubMed1989

Effect of fetal exposure to ultrasound on B cell development in BALB/c mice.

Ultrasound is a major tool for clinical diagnosis, especially during prenatal life. Therefore, it is important that the potential bioeffects of ultrasound be determined. In this report, the effects of ultrasound on the development of B lymphocytes is studied. Pregnant BALB/c mice were exposed to intensities of ultrasound ranging from 0.1-3.0 W/cm2, receiving either a single exposure on day 11, or multiple exposures on days 14, 15, and 18 or 19 of gestation. Fetal livers were removed on day 19 of gestation whereas spleen cells were obtained from 5 and 10 day old neonates. These cell populations were analyzed for: (a) the frequency of B220+ B lineage cells; (b) the frequency of immunoglobulin-positive (Ig+) cells, and (c) the ability to proliferate in response to the B cell mitogen lipopolysaccharide (LPS). None of the tests performed revealed any substantial differences between ultrasound-exposed versus sham-treated control animals. In addition, the development of blood cell types other than B lineage cells remained unaffected by exposure to ultrasound. Therefore, exposure to ultrasound at the intensities used does not appear to hinder hemopoiesis or the normal development of B lymphocytes during fetal and early neonatal life.

Animals↗
PubMed1989

Identification of groups at risk for renal diseases (including nephrotoxicity).

An assessment of the health significance of renal disease due to nephrotoxicity and identification of groups at risk for toxic nephropathy is difficult because the incidence is likely to be underestimated in the available registry data. In more than 50% of all cases of end-stage renal failure, the causality is not known. In end-stage toxic nephropathy, the kidney may show the morphological changes of chronic interstitial nephritis as well as those of chronic glomerulonephritis. Therefore, additional epidemiological data and information on exposure are necessary. Physiological, social and educational factors may aggravate exposure, and the role of multiple exposures is unknown, although individuals at risk are not only those with the highest burden of exposure. Differential sensitivity is explained in part by genetic factors, as shown for abnormal sulphoxidation and slow acetylation. Early identification of groups at risk for nephropathy of clinical significance still relies on the methods of classical nephrology, i.e., measurement of proteinuria or decreased glomerular filtration rate, but several new tests are currently under evaluation.

Drug-Related Side Effects and Adverse Reactions↗
PubMed1994

Radiation exposure from cervical spine radiographs.

Radiation exposure to hospital personnel during 41 cervical spine radiographs of 30 multiply injured patients was prospectively evaluated. A digital dosimeter was attached to the exposed torso of personnel applying upper extremity traction or managing the airway. Radiation exposure was measured during each radiograph. Any exposure of one or more milliroentgen was detectable. No radiograph resulted in a measurable radiation exposure. Multiple radiographs (up to five exposures) also did not register even the minimum recordable exposure, demonstrating that exposure is less than 1.0 mR per radiograph (P < .05). We conclude that hospital personnel, even those applying traction or managing the airway, are not at risk of significant radiation exposure at the time of cervical spine radiographs.

Cervical Vertebrae↗
PubMed1997

Hepatitis C transmission on the north coast of New South Wales: explaining the unexplained.

OBJECTIVE: To determine the routes of hepatitis C virus (HCV) transmission in an Australian community. DESIGN: Questionnaire-based, cross-sectional survey of notified HCV cases. SUBJECTS AND SETTING: All cases notified to the New South Wales North Coast Public Health Unit between 1 January 1993 and 30 September 1994. OUTCOME MEASURES: Frequency of potential transmission exposures (parenteral and sexual); most likely primary exposure; HCV infection rates in sexual partners and offspring. RESULTS: 467 subjects responded (47% of resident cases). Of these, all but one reported actual or potential blood exposures (injecting drug user [IDU], 85%; IDU with sharing of injection equipment, 76%; pre-1990 blood transfusions, 6%; other blood exposures, 8%). Most subjects reported multiple exposures and none reported sexual contact as the only potential exposure. Of 233 sexual partners tested for HCV, 83 were positive; 54 of these were questioned and all had other parenteral exposures. Only three children out of 91 children tested were positive for HCV (two expressing maternal antibodies). CONCLUSIONS: In contrast with previous studies, possible HCV transmission modes were identified for almost all respondents. Most respondents in this community were IDUs. Non-parenteral transmission appeared minimal. Novel approaches to preventing HCV transmission in IDUs are needed.

Adolescent↗
PubMed2006

Immunoreactivity of c-Fos, NGF and its receptor TrkA in the periventricular zone of the rat hypothalamus after open field exposure.

The immunoreactivity (ir) for c-Fos, NGF and TrkA, following an acute and chronic open field stress, were studied in the periventricular zone of rat hypothalamus. Adult rats were divided into three groups: control, exposed to acute (single exposure--15 minutes) and chronic (multiple exposures--15 minutes daily for 21 days) open field stress. In the control rats neurons immunoreactive to c-Fos, TrkA and NGF were found. The number of TrkA- and NGF-ir cells was high, whereas this of c-Fos-ir ones was low. In animals exposed to acute open field stress the number of c-Fos-ir cells in the examined nuclei varied, however it was much higher than that in the control animals. The number of TrkA-ir neurons in all the studied nuclei was also higher than that in the control animals, but the increase of the number of NGF-ir neurons was not observed in supraoptic nucleus. In the animals exposed to chronic open field stress the number of c-Fos-ir cells was increased in comparison to that in the control rats. After chronic stress exposure the number of TrkA-ir neurons in supraoptic nucleus remained high in comparison to that in animals exposed to acute stress, whereas it was decreased in other studied nuclei. No significant differences in the number of NGF-ir cells were observed between the groups exposed to the acute and chronic stress. Observed decrease of c-Fos- and TrkA-ir in the studied nuclei in the animals suffering from chronic stress in comparison with the acute one may indicate the occurrence of habituation phenomenon. This phenomenon does not concern NGF-ir.

Animals↗
PubMed2024

Causal Mediation Analysis for Integrating Exposure, Genomic, and Phenotype Data.

Causal mediation analysis provides an attractive framework for integrating diverse types of exposure, genomic, and phenotype data. Recently, this field has seen a surge of interest, largely driven by the increasing need for causal mediation analyses in health and social sciences. This article aims to provide a review of recent developments in mediation analysis, encompassing mediation analysis of a single mediator and a large number of mediators, as well as mediation analysis with multiple exposures and mediators. Our review focuses on the recent advancements in statistical inference for causal mediation analysis, especially in the context of high-dimensional mediation analysis. We delve into the complexities of testing mediation effects, especially addressing the challenge of testing a large number of composite null hypotheses. Through extensive simulation studies, we compare the existing methods across a range of scenarios. We also include an analysis of data from the Normative Aging Study, which examines DNA methylation CpG sites as potential mediators of the effect of smoking status on lung function. We discuss the pros and cons of these methods and future research directions.

causal inference↗
PubMed1993

Dimethylformamide pharmacokinetics following inhalation exposures to rats and mice.

Whole-body inhalation exposures to N,N-dimethylformamide (DMF) were conducted with rats and mice. The exposure concentrations were 10, 250, and 500 ppm DMF. The exposure routines consisted of single 1-, 3-, or 6-hour exposures and ten 6-hour exposures (ten exposure days in 2 weeks). Area under the plasma concentration curve (AUC) values were determined following exposure for DMF and "N-methylformamide" ["NMF" represented N-methylformamide plus N-(hydroxymethyl)-N-methylformamide (DMF-OH)]. The DMF AUC values increased 8- and 29-fold for rats and mice, respectively, following single six-hour exposures to 250 and 500 ppm DMF. These data are indicative of saturation of DMF metabolism. Peak "NMF" plasma concentrations for rats and mice, following single 6-hour exposures, did not increase as DMF exposure concentrations increased from 250 to 500 ppm. In addition, the "NMF" plasma levels in rats following a single 6-hour 500 ppm DMF exposure did not decay by 24 hours post exposure. These "NMF" plasma data also indicate saturation of DMF metabolism. Multiple exposures to 500 ppm DMF resulted in a 3- and 4-fold reduction in DMF AUC values for rats and mice, respectively, compared to AUC values following a single six-hour 500 ppm DMF exposure. This indicates enhanced metabolism of DMF resulting from multiple 500 ppm DMF exposures and together with saturation of DMF metabolism suggest using exposure levels below 500 ppm in a chronic bioassay. Selected plasma samples were simultaneously assayed for NMF and DMF-OH. The "NMF" values consisted of between 30 to 60 percent DMF-OH depending upon the exposure group (conversely NMF represented 30 to 60 percent of the "NMF" levels). Urinary analysis of all samples revealed DMF-OH represented over 90 percent of the summed DMF, DMF-OH and NMF quantities.

Administration, Inhalation↗
PubMed1995

Airway hyperresponsiveness in workers exposed to low levels of irritants.

The purpose of this study was to assess the association between occupational exposure to low levels of airway irritants, and airway responsiveness to histamine. In 688 male workers, symptom prevalence was assessed according to the British Medical Research Council (BMRC) questionnaire. All subjects performed a 30 s tidal breathing challenge test. Airway hyperresponsiveness (AHR) was defined as a 20% fall in forced expiratory volume in one second (FEV1) at < or = 32 mg.ml-1 histamine. On the basis of job titles and working department, the exposure status of all workers was characterized into seven groups: 1) reference group; 2) white collars; 3) SO2, HCl, SO4(2-); 4) polyester vapour; 5) oil mist and oil vapour; 6) polyamide and polyester vapour; and 7) multiple exposures. Using multiple logistic regression, no association was found between the exposure groups and a higher prevalence of AHR. A higher prevalence was significantly associated with a low FEV1, a history of allergy, and the presence of chronic respiratory symptoms. Subjects in the SO2 group and the oil mist group with < or = 5 exposure years had a lower prevalence of AHR, probably due to pre-employment selection procedures. There was some trend for subjects with more than 5 yrs exposure to polyester vapour and to oil mist and to oil vapour to have a higher prevalence of AHR. Analyses using the dose-response slope according to O'Connor, revealed similar results and provides no additional information. We conclude that no association could be demonstrated between low grade exposure to airway irritants and airway hyperresponsiveness, and that further research is needed to elucidate this relationship.

Adult↗
PubMed1996

Massive hepatic necrosis and death following repeated isoflurane exposure: case report and review of the literature.

Multiple exposures to halothane have been shown to produce hepatic injury and subsequent hepatic failure often leading to death. Isoflurane, a related haloalkane, is considered a nonhepatotoxic alternative to halothane and its potential to cause injury has been greeted with skepticism. Described is a 30-year-old woman who developed hepatic failure and died after being exposed twice to isoflurane. Recent exposure to anesthetic agents must be considered when death is caused by massive hepatic necrosis.

Adult↗
PubMed2001

Ecological risk assessment of multimedia hazardous air pollutants: estimating exposure and effects.

Hazardous air pollutants, some of which have the potential for multimedia distribution, raise several hurdles for ecological risk assessment including: (1) the development of an adequate transport, fate and exposure model; and (2) the selection of exposure-response models that can accommodate multiple exposure routes for ecological receptors. To address the first issue, the EPA Office of Air Quality Planning and Standards has developed TRIM.FaTE, a mass-balance, fate, transport, and ecological exposure model that is a component of the Total Risk Integrated Methodology (TRIM) for air pollutants. In addition to abiotic transfers and transformations, TRIM.FaTE estimates the uptake of a chemical by terrestrial and aquatic organisms with time. Measures of exposure that TRIM.FaTE can provide include: (1) body burdens or tissue concentrations; (2) doses averaged over any time period; or (3) concentrations of chemicals in abiotic media. The model provides the user with the flexibility to choose the exposure-response thresholds or dose-response relationships that are best suited to data availability, routes of exposure, and the mechanism of toxicity of the chemical to an ecological receptor. One of the challenges of incorporating TRIM.FaTE into a risk assessment methodology lies in defining a streamlined model simulation scenario for initial screening-level risk assessments. These assessments may encompass multiple facilities that emit a variety of pollutants near diverse ecosystems. The information on ecological risk assessment methodology that is described is applicable to the EPA Residual Risk Program with emphasis on multimedia pollutants and the role of TRIM.FaTE.

Air Pollutants↗
PubMed1992

Agents that cause enlargement of sebaceous glands in hairless mice. II. Ultraviolet radiation.

We have developed a murine model to measure the effects on sebaceous glands of ultraviolet (UV) radiation. Hairless mice were irradiated with Westinghouse FS-40 tubes filtered to attenuate the radiation below 290 nm. Emission was mainly in the UVB range (peak, 313nm). Single and multiple exposures were given with fractions or multiples of one minimal erythemal dose (MED). Biopsies, fixed for light microscopy, were stained with H & E. Under high power, sebocytes of 30 glands per specimen were counted and the means determined. A single exposure of 1 MED caused a significant increase in sebocyte count, as did thrice-weekly exposures to 0.5 MED for 3 weeks. One 3-MED exposure produced sebocyte necrosis, yet 30 exposures at 4 MED failed to ablate the glands. In both cases there was rebound enlargement which had not returned to control levels by the end of the studies (24-30 weeks). Prolonged irradiation produced maximum enlargement in a few weeks. Thus, in a manner similar to other skin components, the response of sebaceous glands to UV radiation is one of hyperplasia.

Animals↗
PubMed1991

Characterization of allergen-induced bronchial hyperresponsiveness and airway inflammation in actively sensitized brown-Norway rats.

Bronchial responsiveness to inhaled acetylcholine (ACh) and inflammatory cell recruitment in bronchoalveolar lavage fluid (BALF) were studied in inbred Brown-Norway rats actively sensitized to, and later exposed to, ovalbumin (OA). We examined animals 21 days after initial sensitization at 18 to 24 hours, or 5 days after a single challenge, or after the last of seven repeated exposures administered every 3 days. BALF was examined as an index of inflammatory changes within the lung. Animals repeatedly exposed to OA aerosols had an increased baseline lung resistance and a significant increase in bronchial responsiveness to inhaled ACh compared to control animals at both 18 to 24 hours and 5 days after the last OA exposure. Sensitized animals receiving a single OA aerosol also demonstrated bronchial hyperresponsiveness (BHR) to inhaled ACh (p less than 0.01) at 18 to 24 hours of a similar order as the multiple-exposed group. There was a significant increase in eosinophils, lymphocytes, and neutrophils in BALF at 18 to 24 hours but not at 5 days after single or multiple exposure to OA aerosol in the sensitized groups. Control animals demonstrated no changes in bronchial responsiveness, although a small but significant increase in inflammatory cells was observed compared to saline-only treated animals. There was a significant correlation between bronchial responsiveness and eosinophil counts in the BALF in the single allergen-exposed group (Rs = 0.68; p less than 0.05). We conclude that (1) BHR after allergen exposure in sensitized rats is associated with the presence of pulmonary inflammation but persists despite the regression of inflammatory cells in BALF after multiple OA exposures, and (2) this rat model has many characteristics of human allergen-induced BHR.

Acetylcholine↗
PubMedDate not supplied

Protein expression changes associated with radiation-induced neoplastic progression of human prostate epithelial cells.

Carcinogenic progression in most epithelial systems is a multistep process and presents as numerous (un)stable intermediate stages prior to the development of a fully malignant phenotype. Recently, we reported the neoplastic transformation of an SV40 immortalized, neonatal human prostate epithelial cell line (267B1) by multiple exposures to X-rays [1, 2]. The parental 267B1 cells acquired anchorage-independence and exhibited morphological transformation following exposure to two consecutive doses of 2 Gy. Exposure of either the parental 267B1 cells or the anchorage-independent derivatives (F3-SAC) to a total dose of 30 Gy of X-rays yielded tumorigenic transformants (267B1-XR and 267B1-SXR, respectively). All of these radiation-treated derivatives (F3-SAC, 267B1-XR, and 267B1-SXR) were characterized by reduced cell size and poorly organized actin stress fibers [2, 3]. The present study examines the protein expression changes associated with cytoskeletal alterations during the different steps of neoplastic progression induced by X-rays in the in vitro human prostate cell system. This analysis was achieved by using the high resolving power of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) in the 267B1, F3-SAC, 267B1-XR, and 267B1-SXR cells. We report changes in the expression of gelsolin in the partially transformed, anchorage-independent, nontumorigenic (F3-SAC) cells and a progressive loss of expression of tropomyosin isoforms (TM-1 and TM-3), and myosin light chain-2 (MLC-2) in the tumorigenic (267B1-XR; 267B1-SXR) cells, respectively. In contrast, our results demonstrate that the levels of the small GTP-binding protein Rho-A, an active participant in the actin stress fiber organization, are not altered during neoplastic progression of these 267B1 cells. Thus the changes in synthesis of gelsolin, tropomyosins, and MLC-2 provide a rationale for the alterations in the actin stress fiber formation and reduction in cell size during the exposure of prostate epithelial cells to multiple doses of X-rays.

Actins↗
PubMed2003

Overview and characteristics of some occupational exposures and health risks on offshore oil and gas installations.

This review considers the nature, and recognition and control, of health risks in the offshore oil and gas industry from the occupational hygiene point of view. Particular attention is given to the changes in the nature of exposure and control of inhalation risks from substances hazardous to health in the UK sector, but other risks (e.g. dermatitis, noise and vibration) are also considered. The amount of published information on exposure to these hazards in the sector, or indeed on long-term health outcomes of working offshore, is limited. The approach taken to occupational health and hygiene in the sector has to be set in the context of the challenge of working in a remote and hostile environment where attention to safety and the need for emergency response to acute, rather than chronic, medical events are vital. However, changes in attitudes towards occupational health in the sector, legislation, the impact of environmental protection requirements and technology have all contributed to increasing the attention given to assessment and control of chemical and physical hazards. The health risks and benefits associated with the abandonment of installations, the application of new technologies, recovery of oil from ever deeper waters, lower staffing levels, environmental changes, the ageing workforce and the recognition of exposure patterns needing further attention/control (sequential multiple exposures, smaller workforce, peak/short-term exposures, etc.) are other current and future occupational hygiene challenges.

Air Pollutants, Occupational↗
PubMed2006

Occupational exposure to acidic chemicals and occupational dental erosion.

OBJECTIVE: This study investigated the association between occupational acidic chemicals (ACs) exposure and occupational dental erosion. METHODS: A cross-sectional study was conducted in which three dentists surveyed 951 subjects from 42 factories using five types of ACs below Korean Threshold Limit Values (K-TLVs). Subjects agreed to participate by a written consent; 519 were acid exposed workers and 431 were non-exposed. The modified ten Bruggen Cate's criteria was used to classify erosion. Length and type of exposure to ACs were assessed using questionnaires. Logistic regression analysis including interaction terms was applied. RESULTS: ACs exposure was associated with erosion severity. Multiple exposures to ACs were found to be strongly associated with severe erosion. Interaction between wearing masks and AC exposure was significant. CONCLUSIONS: This study showed a clear association between AC exposure below K-TLVs and erosion. Hence, the authors propose to lower K-TLVs of five types of ACs.

Acids↗