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At least 163 records · Page 9Linked to original sources
PubMed2006

Studies of multiple sclerosis in communities concerned about environmental exposures.

Multiple sclerosis (MS) is an autoimmune disease that differentially affects women, people 30-60 years old, and Caucasians. Evidence indicates that it is a complex disease determined by both environmental factors and genetic susceptibility. People across the United States have expressed concern about perceived clusters of MS in their communities and the role of environmental exposures in the development of the disease. The Agency for Toxic Substances and Disease Registry (ATSDR) has funded several studies to address this issue, including a cluster investigation, several prevalence studies, and a case-control study. The cluster investigation illustrated that there are few data regarding the number of individuals with MS in the United States. Prevalence studies were conducted in Ohio, Missouri, and Texas to address this deficiency. The results support a regional difference in MS prevalence, although the reason for this difference is unclear. The results also underscore the need for additional epidemiological information about the distribution of MS in other areas of the United States and information on the underlying etiology of the disease. A case-control study is currently being conducted to examine potential risk factors for MS, including the role of environmental exposures and genetic susceptibility. Future research on MS should focus on large-scale studies and include collaboration among researchers with varied fields of expertise, such as epidemiology, neurology, and genetics.

Adult↗
PubMed2000

Outcomes of single versus multiple trauma exposure in a screening sample.

Most studies ignore prior trauma exposure when evaluating outcomes of target events. This study explored symptom severity associated with different types of traumatic experiences occurring alone and with multiple exposure. The Stressful Life Events Screening Questionnaire categorized 1,909 sophomore women into groups including no trauma exposure, exposure to a serious non-Criterion A event only, exposure to several unique noninterpersonal and interpersonal events, and exposure to multiple interpersonal events. Women with noninterpersonal trauma did not differ from those without trauma on the Trauma Symptom Inventory. Only interpersonal trauma and non-Criterion A events were associated with elevated symptoms; multiple-exposure participants had significantly higher symptoms than all other groups. Complex trauma histories should be accounted for, even in studies of one target event.

Adolescent↗
PubMed2004

The effect of a novel smoking system--Accord--on ongoing smoking and toxin exposure.

Multiple potentially reduced exposure products (PREPs) are being introduced to the market, yet little is known about how they will be used and what their public health impact might be. To determine the impact of one such PREP--Accord--on ongoing smoking and toxin exposure, 11 smokers of light cigarettes were required to use increasing amounts of Accord (5, 10, and 15 per day) with the option of using their traditional cigarettes. Accord suppressed ongoing cigarettes per day and carbon monoxide (CO), but not cotinine, in a dose-dependent manner. Smoking 15 Accord per day decreased the number of traditional cigarettes smoked by 32% (-8.6 cigarettes per day) and CO levels by 27% (-5.9 ppm). However, Accord did not function as a perfect (i.e., one to one) substitute for cigarettes because the total number of nicotine products (Accord plus usual brand) per day increased by 24%. Participants believed that Accord was safer than traditional cigarettes but rated Accord as ineffective at suppressing cravings for cigarettes. These findings suggest that use of Accord results in significant decreases in cigarettes smoked and CO exposure. Whether these reductions will translate into health benefits or endure beyond 2 weeks is unknown. Because most PREPs will probably be used along with traditional cigarettes, their net health impact is a function of not only their toxicological profile but also their effect on ongoing smoking.

Adult↗
PubMedDate not supplied

The environment of poverty: multiple stressor exposure, psychophysiological stress, and socioemotional adjustment.

The one in five children growing up in poverty in America have elevated risk for socioemotional difficulties. One contributing factor to their elevated risk may be exposure to multiple physical and psychosocial stressors. This study demonstrated that 8- to 10-year-old, low-income, rural children (N = 287) confront a wider array of multiple physical (substandard housing, noise, crowding) and psychosocial (family turmoil, early childhood separation, community violence) stressors than do their middle-income counterparts. Prior research on self-reported distress among inner-city minority children is replicated and extended among low-income, rural White children with evidence of higher levels of self- and parent-reported psychological distress, greater difficulties in self-regulatory behavior (delayed gratification), and elevated psychophysiological stress (resting blood pressure, overnight neuroendocrine hormones). Preliminary mediational analyses with cross-sectional data suggest that cumulative stressor exposure may partially account for the well-documented, elevated risk of socioemotional difficulties accompanying poverty.

Affective Symptoms↗
PubMed2002

Necessity to establish new risk assessment and risk communication for human fetal exposure to multiple endocrine disruptors in Japan.

Our recent study clearly shows that fetuses are exposed to multiple chemicals including endocrine disruptors in Japan. Although the embryo and fetus stages are the most sensitive period to chemicals in humans' life cycle, the health effects of the chemicals such as endocrine disruptors to them are largely unknown. The conventional risk assessment method cannot assess the risk to fetuses precisely. Now we need a new risk assessment, in which the target is fetuses and not the adults, in addition to the conventional risk assessment. At the same time, we also need a new strategy to practically eliminate the risk for the future generations. To make the strategy effective, we suggest a new approach to reduce the risk and avoid the possible adverse health effects, using primary, secondary and tertiary preventions as they are used in public health. We also suggest a new concept of "pre-primary prevention" to reduce the risk for fetuses. Furthermore, to make this method even more practical, we suggest a new risk communication method. In this paper, we present a framework of risk avoidance of multiple chemical exposure to fetuses.

Congenital Abnormalities↗
PubMedDate not supplied

Long-term learning deficits and changes in unlearned behaviors following in utero exposure to multiple daily doses of cocaine during different exposure periods and maternal plasma cocaine concentrations.

Although the possible behavioral neurotoxic effects of in utero exposure to cocaine have been the subject of numerous experiments, only a limited number of different types of animal models of cocaine exposure, critical periods, or long-term effects of such exposures have been investigated. In the present experiment, the effects of multiple daily SC exposures to cocaine (20 mg/kg/dose x 5 doses per day) were investigated when administered to gravid Sprague-Dawley CD rats on embryonic days E7-12 or E13-18 compared to weight-matched, vehicle injected, pair-fed controls. Effects of exposure were assessed on general development, olfactory orientation behavior, early locomotion, startle reactivity, spontaneous motor activity, and learning on two different tasks (Morris and Cincinnati water mazes). The multiple cocaine dosing regimen produced maternal peak serum concentrations of cocaine 3 times higher than that of a single dose (approximately 1550 vs. approximately 550 ng/mL). Early-exposed cocaine offspring had lower olfactory orientation scores and reduced postweaning rearing and hole-poke motor activity, whereas late-exposed cocaine offspring had increased postweaning locomotor, rearing, and hole-poke activity. On the Morris hidden platform maze, the cocaine early-exposed females had longer latencies on acquisition than controls. On the Cincinnati multiple-T water maze, the early-exposed cocaine females and the late-exposed cocaine males had increased errors, whereas the early-exposed cocaine males had reduced errors. The effects on measures of learning, when taken together, and in light of their being in the early-exposed group, suggest that embryonic cocaine exposure may have subtle effects on cognition in the offspring as adults. Such effects represent a form of neurotoxicity not previously associated with prenatal cocaine exposure.

Animals↗
PubMed1993

Adverse reproductive outcomes and occupational exposures among nurses: an investigation of multiple hazardous exposures.

1. The increasing numbers of pregnant women and women of childbearing age who are employed and exposed to hazardous substances pose occupational health concerns. 2. The findings of this study indicate the importance of not minimizing concern about exposure to radiation. Radiation monitoring should be implemented to a greater extent, and methods to measure low dose chronic radiation exposure should be developed. 3. Synergy between the adverse reproductive effects from multiple workplace factors among nurses, including but not limited to radiation, video display terminal use, and chemotherapeutic agents, warrants further evaluation.

Adolescent↗
PubMed2000

Disposition of radioactivity in fischer 344 rats after single and multiple inhalation exposure to [(14)C]Octamethylcyclotetrasiloxane ([(14)C]D(4)).

The retention, distribution, metabolism, and excretion of [(14)C]octamethylcyclotetrasiloxane (D(4)) were studied in Fischer 344 rats after single and multiple exposures to 7, 70, or 700 ppm [(14)C]D(4). Subset groups were established for body burden, distribution, and elimination. Retention of inhaled D(4) was relatively low (5-6% of inhaled D(4)). Radioactivity derived from [(14)C]D(4) inhalation was widely distributed to tissues of the rat. Maximum concentrations of radioactivity in plasma and tissues (except fat) occurred at the end of exposure and up to 3 h postexposure. Maximum concentrations of radioactivity in fat occurred as late as 24 h postexposure. Fat was a depot, elimination of radioactivity from this tissue was much slower than from plasma and other tissues. With minor exceptions, there were no consistent gender effects on the distribution of radioactivity and the concentrations of radioactivity were nearly proportional to exposure concentration over the exposure range. Excretion of radioactivity was via exhaled breath and urine, and, to a much lesser extent, feces. Urinary metabolites included dimethylsilanediol and methylsilanetriol plus five minor metabolites. Relative abundance of these metabolites was the same from every test group. Elimination was rapid during the first 24 h after exposure and was slower thereafter (measured up to 168 h postexposure). In singly-exposed female (but not male) rats, small dose-dependent shifts in elimination pathways were seen. After multiple exposures, the elimination pathways were dose- and gender-independent. These data define possible pathways for metabolism of D(4) and allow estimation of the persistence of D(4) and/or its metabolites in rats.

Administration, Inhalation↗
PubMedDate not supplied

[Multiple occupational exposure to solvents].

This article review papers published over the last 20 years on multiple occupational exposure to solvents. At low-levels of exposure the toxicokinetic interferences between solvents have generally not been observed in man and presumably a threshold limit exists. Conversely, at exposure levels close to the "limit values" metabolic interference has sometimes been observed and the behaviour of the biological indicators differs from what would be expected. Toxicodynamic interference between solvents can give rise to additive, potentiation, synergistic, antagonistic effects. For the identification of "limit values", it has generally been suggested in the literature that the possible effects deriving from multiple exposure be considered as additive. However, numerous potentiation effects have frequently been reported for combined exposure to substances of widespread use. In this paper lists of multiple exposure in which the doses of the substances, the types of interferences and the behaviour of the biological levels have been drawn up and proposed as a tool for easy consultation.

Alcohol Drinking↗
PubMed2004

Multiple vaginal exposures to low doses of R5 simian-human immunodeficiency virus: strategy to study HIV preclinical interventions in nonhuman primates.

A nonhuman-primate model of human immunodeficiency virus type 1 (HIV-1) infection that more closely emulates human heterosexual transmission by use of multiple exposures to low doses of virus is critical to better evaluate intervention strategies that include microbicides or vaccines. In this report, we describe such a system that uses female pig-tailed macaques exposed vaginally to a CCR5-using simian-human immunodeficiency virus (SHIV(SF162P3)) at weekly intervals. Results of dose-titration experiments indicated that 3 once-weekly exposures to 10 tissue culture infectious doses of SHIV(SF162P3) resulted in consistent transmission of virus and establishment of systemic infection. The efficacy of cellulose acetate phthalate (CAP) as a vaginal microbicide was evaluated by applying it to the vaginal vault of macaques (n = 4) 15 min before each weekly exposure to SHIV(SF162P3). One conclusion that can be drawn from the data derived from multiple exposures to virus is that CAP prevented infection in 12 of 13 possible chances for infection, over the course of 39 total exposures. Our findings provide a basis to refine monkey models for transmission of HIV-1, which may be relevant to preclinical evaluation for therapeutic interventions.

Animals↗
PubMed2006

Cigarette smoke induces cellular senescence.

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States, and cigarette smoking is the major risk factor for COPD. Fibroblasts play an important role in repair and lung homeostasis. Recent studies have demonstrated a reduced growth rate for lung fibroblasts in patients with COPD. In this study we examined the effect of cigarette smoke extract (CSE) on fibroblast proliferative capacity. We found that cigarette smoke stopped proliferation of lung fibroblasts and upregulated two pathways linked to cell senescence (a biological process associated with cell longevity and an inability to replicate), p53 and p16-retinoblastoma protein pathways. We compared a single exposure of CSE to multiple exposures over an extended time course. A single exposure to CSE led to cell growth inhibition at multiple phases of the cell cycle without killing the cells. The decrease in proliferation was accompanied by increased ATM, p53, and p21 activity. However, several important senescent markers were not present in the cells at an earlier time point. When we examined multiple exposures to CSE, we found that the cells had profound growth arrest, a flat and enlarged morphology, upregulated p16, and senescence-associated beta-galactosidase activity, which is consistent with a classic senescent phenotype. These observations suggest that while a single exposure to cigarette smoke inhibits normal fibroblast proliferation (required for lung repair), multiple exposures to cigarette smoke move cells into an irreversible state of senescence. This inability to repair lung injury may be an essential feature of emphysema.

Ataxia Telangiectasia Mutated Proteins↗
PubMed1995

The effects of multiple UV exposures on HIV-LTR expression.

Previous studies have shown that cellular stress agents such as UV radiation induce transcription from the long terminal repeat (LTR) of the human immunodeficiency virus (HIV). Using HeLa cells stably transfected with the HIV-LTR sequence, which transcriptionally drives the chloramphenicol acetyl transferase (CAT) reporter gene, we examined the effects of multiple exposures to UVC (254 nm) on HIV-LTR-CAT expression. Low doses (< or = 5 J m-2) had no effect on CAT expression, but up to 29-fold induction was observed with 10 J m-2 when cells were harvested 48 h after completion of the exposure. Little difference was noted in induction levels when cells were exposed to one 25 J m-2 dose, viable cells were harvested at 24 h, 48 h or 72 h, and cell lysates were assayed for CAT expression. Two sequential 12.5 J m-2 exposures, given 24 h apart, resulted in an additive effect on CAT expression; these two exposures produced CAT activity equivalent to that induced following a single 25 J m-2 dose. This additive effect was not evident at the lower doses (< or = 5 J m-2) or at the higher doses. Maximal induction was observed using doses from 25 to 37.5 J m-2. Multiple exposures with either the low (< or = 5 J m-2) or high doses (> 25 J m-2) did not result in an additive effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Chloramphenicol O-Acetyltransferase↗
PubMed2002

Cold tolerance: behavioral differences following single or multiple cold exposures.

Previous research has demonstrated that repeated exposure to cold water results in cold tolerance. The present set of experiments examined whether spontaneous behavioral activity and the rate of rewarming differed between cold tolerant and nontolerant rats. Animals receiving six cold exposures (one per day) were compared to subjects receiving a single cold exposure but cooled to match the final day temperature of the six-exposure group. Immediately following the final or only cold exposure, activity was measured by an activity monitor (Exp. 1) or was videotaped and scored by an independent observer (Exp. 2). Furthermore, rats' temperatures were monitored for 90 min (Exp. 2) and 60 min (Exp. 3) following the activity measurement. The results indicated that cold-tolerant rats exhibited activity similar to normal, noncooled subjects, whereas the activity in the single exposure group was impeded. Moreover, rats in the multiple exposure groups rewarmed more quickly than subjects in the single exposure condition. The third experiment also examined if the procedures of Experiments 1 and 2 resulted in associative cold tolerance. Experiment 3 replicated earlier findings, which have shown that exposure to the same cold stimulus in an altered context resulted in a loss of tolerance. These findings suggest that the processing of contextual stimuli is necessary for the acquisition of cold tolerance and that behavioral activity and rewarming rates can be used as alternative measures of cold tolerance.

Animals↗
PubMed1998

Single blood donor exposure programme for preterm infants: a large open study and an analysis of the risk factors to multiple donor exposure.

UNLABELLED: As the need for blood transfusions of very preterm infants remains considerable, various strategies are considered to minimize exposure to multiple blood donors along with blood wastage. In a large population of very preterm infants born between 24 and 31 weeks' gestation, we undertook an open study to assess the efficacy of a single blood donor exposure programme and to determine, among the population enrolled in this programme, the risk factors for exposure to multiple donors. One hundred and forty-two neonates were included in a single donor exposure programme with a 35-day expiry date blood unit. Though no inflation in the total number of transfusions was noticed, there was a 55% overall reduction in the total number of required donors. To determine the risk factors for exposure to multiple donors in this population, 114 neonates alive after the expiry date of the first unit of packed red blood cells were selected. The greatest and the most extending transfusion requirements were observed in very preterm infants born before 28 weeks' gestation and in those born after but with an intra-uterine growth retardation below the 10th percentile. Indeed, 70% of those high-risk infants were exposed to a second blood donor and more than 85% of the group exposed to a second donor belonged to this high-risk population. CONCLUSION: Neonates with a very high risk of a more-than-one donor exposure were born before 28 weeks' gestation or between 28 and 31 weeks but with an intra-uterine growth retardation below the 10th percentile.

Blood Donors↗
PubMed1994

Multiple +Gz exposures cause brain edema in rats.

The most serious effect of high sustained +Gz (head-to-foot inertial load) known to occur in pilots of high performance aircraft is +Gz-induced loss of consciousness (G-LOC), which may result in pilot incapacitation and subsequent loss of life. G-LOC is believed to occur due to a critical reduction in cerebral blood flow (CBF). Recently, using a small animal centrifuge (SAC), we showed that +Gz exposure causes global cerebral ischemia in a rodent animal model. Since ischemia, depending upon the severity and duration, has been associated with increased brain water content or edema, the present study was undertaken. Rats were exposed to six exposures of either +25 Gz (30 s each) or +10 Gz (2 min each) in the SAC at +20 Gz.s-1 G onset rate. The appearance of G-LOC was monitored by the flattening of the electroencephalography (EEG) brain wave recording. G-LOC was observed at 101 +/- 46 and 19.2 +/- 5 s during +10 and +25 Gz exposures, respectively. The brains from these animals were removed 15 min to 24 h after the +Gz exposure and analyzed for edema formation (increase in the percentage of tissue water), metabolites, and cerebral blood volume (CBV). A significant decrease in glucose and an increase in lactate concentration were observed during +Gz exposure. Edema formation was observed 15 min after six exposures of either +10 or +25 Gz. A slight but significant decrease in CBV was also observed in rats exposed to six +10 Gz exposures. Edema formation was transient and resolved within 24 h. We concluded that multiple exposures of either +25 Gz, short duration or +10 Gz, long duration, that resulted in G-LOC, can cause cytotoxic brain edema which probably results from tissue hyperosmolality due to metabolic changes and accumulation of lactate during ischemia.

Acceleration↗
PubMed2001

Using dose addition to estimate cumulative risks from exposures to multiple chemicals.

The Food Quality Protection Act (FQPA) of 1996 requires the EPA to consider the cumulative risk from exposure to multiple chemicals that have a common mechanism of toxicity. Three methods, hazard index (HI), point-of-departure index (PODI), and toxicity equivalence factor (TEF), have commonly been considered to estimate the cumulative risk. These methods are based on estimates of ED(10) (point of departure) and reference doses from the dose-response functions of individual chemicals. They do not incorporate the actual dose-response function of the mixture from multiple chemical exposures. Dose addition is considered to be an appropriate approach to cumulative risk assessment because it assumes that the chemicals of interest act in accordance with a common mode of action (a similar action). This paper proposes a formal statistical procedure to estimate the cumulative risk by fitting the dose-response model of the mixture under dose addition. The relative potency between two chemicals is estimated directly from the joint dose response model of the mixture. An example data set of four drugs representing four chemicals is used to illustrate the proposed procedure and compare it to the HI, PODI, and TEF methods.

Dose-Response Relationship, Drug↗
PubMedDate not supplied

Multiple chemical exposures: synergism vs. individual exposure levels.

Exposure to single chemicals is known to produce congenital malformations in both pregnant animals and humans exposed at sufficiently high intensity. However, real life involves multiple, simultaneous exposures. Using as a database the 43 multiple chemical exposure studies located by Nelson (Teratology 49:33-71; 1994) where synergism was reported, we explored the degree to which such concerns may be realistic from the viewpoint of the current standard developmental toxicity safety evaluation process. Focusing on the assessment of the lowest tested dose of a given agent participating in synergistic activity as compared to its threshold level for eliciting toxicity when administered alone, we found that while the availability of adequate data was limited, all cases, with the possible exception of one, demonstrated synergistic toxic expression only when at least one, and usually both, compounds were used at or above their individual threshold for toxicity. These findings suggest that in animals such phenomena of synergistic chemical interactions are likely to occur only when at least one and more likely both agents are administered at or above their individual threshold for toxicity. To the extent animal studies are predictive of human developmental hazards due to single chemical exposures, available data do not establish multiple chemical exposures as a major human developmental concern.

Animals↗
PubMed2005

Miotic tolerance to sarin vapor exposure: role of the sympathetic and parasympathetic nervous systems.

O-isopropyl methylphosphonofluoridate, also known as sarin or GB, is a highly toxic organophosphorous compound that exerts its effect by inhibiting the enzyme acetylcholinesterase. While the effects of a single exposure to GB vapor are well characterized, the effects of multiple exposures to GB vapor are less clear. Previous studies in the rat and guinea pig have demonstrated that multiple exposures result in tolerance to the miotic effect of nerve agents. The aim of the present study was to examine potential mechanisms responsible for tolerance to the miotic effect of GB vapor that has been observed in the rat after multiple exposures. Multiple whole-body inhalation exposures to GB vapor were conducted in a dynamic airflow chamber. Exposures lasted 60 min and each of the three exposures occurred at 24-h intervals. The results of the present study demonstrate that the alpha-adrenergic antagonist phentolamine and the beta-adrenergic receptor antagonist propranolol did not affect the development of tolerance to the miotic effect of GB vapor, suggesting that enhanced sympathetic tone to the eye is not responsible for the observed tolerance. Administration of atropine before the first exposure prevented the tolerance to the miotic effect of GB vapor after the third exposure, suggesting that the tolerance is the result of muscarinic receptor desensitization secondary to receptor stimulation. The present study extends the findings of previous studies to strengthen the hypothesis that the miotic tolerance observed in the rat upon repeated exposure to nerve agents is due to desensitization of muscarinic acetylcholine receptors located on the pupillary sphincter.

Adrenergic alpha-Antagonists↗