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At least 1,171 records · Page 65Linked to original sources
PubMed2000

Effect of single versus multiple courses of antenatal corticosteroids on maternal and neonatal outcome.

OBJECTIVE: Treatment of pregnant mothers with a single course of antenatal corticosteroids significantly reduces neonatal mortality and morbidity. Multiple weekly courses are often given. However, the safety and efficacy of repeated courses of antenatal corticosteroids have not been adequately studied. STUDY DESIGN: A retrospective study was performed for 609 mothers and their 713 infants who were treated with 1 to 12 courses of antenatal corticosteroids. Data for 369 singleton preterm infants born at < or =34 weeks' gestation, 210 multiple gestations, and 134 infants delivered at > or =35 weeks' gestation were analyzed separately. RESULTS: The incidence of respiratory distress syndrome was 45% for single-course and 35% for multiple-course groups (P =.005; odds ratio, 0.44; 95% confidence interval, 0.25-0.79). The multiple-course group also had significantly less patent ductus arteriosus (20% vs 13%; P =.016). Incidence of death before discharge and other neonatal morbidities were similar. The multiple-course group had a reduction of 0.46 +/- 0.19 cm in head circumference at birth (P =.013) when adjusted for gestational age and preeclampsia. The 2 groups had similar birth weights. Infants born at > or =35 weeks' gestation, multiple-gestation infants, and infants who were born >7 days after the last corticosteroid dose had similar outcomes, regardless of the number of courses they received. Mothers treated with multiple courses compared with a single course had a significantly higher incidence of postpartum endometritis (P =.013), even though they had a lower incidence of prolonged rupture of membranes (24% vs 33%, P =.06) and similar cesarean delivery rates. CONCLUSION: Exposure to multiple courses of antenatal corticosteroids compared with a single course resulted in a significant reduction in the incidence of respiratory distress syndrome in singleton preterm infants delivered within a week of the last corticosteroid dose. This was associated with a reduction in birth head circumference and an increased incidence of maternal endometritis. Whether the potential benefits of repeated therapy clearly outweigh the risks will ultimately be determined in randomized prospective controlled trials.

Adrenal Cortex Hormones↗
PubMed1982

The role of wildlife species in the assessment of biological impact from chronic exposure to persistent chemicals.

Assessments of chemical toxicity have regularly placed reliance upon experimental studies which employ environmentally unrealistic exposure regimes. This approach ignores the long-term low-level nature of environmental exposure which facilitates the development of factors which modify the toxicity of such chemicals. Examples of such adaptive mechanisms will be taken from the author's own studies. Factors discussed include the development of protective trace element interactions in target organs, the induction of specific metal-binding proteins, and the alteration of the distribution of chemicals at the organ and organelle level. Exposure-response investigations in wildlife are not restricted to the organism level and the impact of an environmentally released chemical upon breeding success and population dynamics can also be investigated. Disadvantages and problems associated with this kind of study, such as multiple pollutant exposure and variability in response, will also be considered.

Animal Population Groups↗
PubMed1995

Brain tumor and exposure to pesticides in humans: a review of the epidemiologic data.

We examined the relationship between exposure to pesticides and the subsequent development of brain tumors in adults through a critical review of the literature. The results of retrospective case-control studies are conflicting, in part because of biases in the selection of patients and controls, poor definition and ascertainment of the nature and extent of the exposure to pesticides, and a non-uniform approach to the collection of antecedent information. A number of the studies evaluated farmers as a group exposed to pesticides; however, inference about cancer incidence in farmers may reflect not only their possible exposure to pesticides, but also exposure to petrochemical products, exhaust fumes, mineral and organic dusts, and biological exposure to animals and microbes. The great majority of the cohort studies of chemical workers employed in the manufacture of pesticides did not indicate an excess of brain cancer mortality. There have been few cohort studies of pesticide applicators and these revealed elevated but non-significant relative risks for excess mortality due to brain cancer. Existing data are insufficient to conclude that exposure to pesticides is a clear risk factor for brain tumors. Given the conflicting results reported for farmers and pesticide applicators and their contrast to chemical workers, it seems more plausible that exposure to multiple agents and/or other factors, such as genetic predisposition, are most relevant with respect to brain tumor pathogenesis.

Adult↗
PubMed2026

Fluoride as a Modifier of Metallome Homeostasis: A Systematic Review of Animal Studies.

Fluoride is widely used for caries prevention due to its effects on mineralized tissues, yet its potential role as a modifier of systemic metal homeostasis remains insufficiently explored. This systematic review synthesizes preclinical evidence on the association between fluoride exposure and changes in metal and semi-metal concentrations across biological matrices. A comprehensive search strategy was conducted across major databases without language or date restrictions, following SyRF, CAMARADES and PRISMA 2020 guidelines. Thirty-one animal studies were included, encompassing multiple species, exposure conditions and analytical approaches. Despite substantial methodological heterogeneity, consistent patterns emerged. Fluoride exposure was associated with element-specific redistribution of the metallome rather than uniform change. Essential elements were predominantly depleted, most consistently zinc, copper and manganese, whereas the toxic metals lead and cadmium tended to be retained. This contrast between homeostatically regulated essential elements that are lost and non-regulated toxic metals that accumulate supports the hypothesis that fluoride differentially modifies the distribution and retention of co-existing elements. The novelty of this review lies in integrating metallomic outcomes across experimental models, highlighting fluoride as a potential systemic modulator rather than a tissue-specific agent. Although variability in study design and risk of bias limits causal inference, the consistent directionality of findings across models reinforces their biological plausibility and translational relevance.

Animals↗
PubMed1984

Multiplicative effect of inhaled plutonium oxide and benzo (a) pyrene on lung carcinogenesis in rats.

This study describes the effect of intratracheal instillations (2 X 5 mg) of benzo(a)pyrene (B(a)P) on lung carcinogenesis in rats which had previously inhaled different levels of 239 plutonium oxide (220, 630, 6300 Bq, initial lung burden). Survival decreased with increasing PuO2 exposure and additional B(a)P exposure. The incidence of malignant lung tumours, adjusted for differences in survival, increased in a dose-related fashion with PuO2 dose and was elevated in the presence of additional B(a)P exposure. A multiplicative relative risk model was found to describe reasonably well the observed joint effect. The practical implications of these findings are discussed.

Administration, Intranasal↗
PubMed1996

Correlates of protection in HIV infection and the progression of HIV infection to AIDS.

Exposure to human immunodeficency virus (HIV) can result in HIV infection which is defined by seroconversion and the detection of HIV-specific antibodies. Nevertheless, in every cohort at risk for HIV infection, individuals are present in whom seroconversion is not observed despite multiple documented exposures to HIV. Recent studies have shown that HIV-specific T-lymphocytes are present in the peripheral blood of these HIV-exposed seronegative individuals, suggesting that cell-mediated immunity (CMI) could have a protective role in the prevention of HIV infection. In most individuals who seroconvert, HIV infection is followed by a long period of clinically asymptomatic latency which ultimately results in the development of acquired immunodeficency syndrome (AIDS). Although this progression is observed in the majority of HIV-infected individuals, individuals exist who are asymptomatic and have relatively high CD4 counts despite long-lasting HIV infection. Analogous to that observed in seronegative HIV-exposed individuals, strong HIV-specific CMI seems to be characteristic of these HIV-seropositive (HIV+) long-term non-progressors (LTNP). Because strong HIV-specific CMI is present in HIV-seronegative individuals exposed to HIV and in HIV+ LTNP, we believe that HIV-specific CMI may be the main correlate of protection against HIV infection and against the progression of HIV infection to AIDS.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Effects of varied-stimulus exposure training on fear reduction and return of fear.

The current investigation assessed the relative treatment benefits of persistence with one specific stimulus vs exposure to multiple versions of a stimulus. The study was a 2 (type of stimulus) x 3 (assessment occasion) design, in which two spider-fearful groups (N = 28) were compared across three different occasions: pre-treatment, post-treatment, and follow-up. Exposure trials were conducted with the same tarantula for participants in the control group, whereas experimental participants were exposed to four novel tarantulas. As predicted, the control group demonstrated significantly more habituation than the experimental group across exposure trials, yet showed a clear return of fear in response to a control spider at a 3-week follow-up assessment whereas the experimental group showed no increase in fear. These findings offer support for the beneficial effects of varying the stimulus during exposure, and challenge the reliance on indices of fear activation and habituation as accurate signals of the permanence of fear reduction.

Adult↗
PubMed2004

Apoptotic cell and phagocyte interplay: recognition and consequences in different cell systems.

Cell death by apoptosis is characterized by specific biochemical changes, including the exposure of multiple ligands, expected to tag the dying cell for prompt recognition by phagocytes. In non-pathological conditions, an efficient clearance is assured by the redundant interaction between apoptotic cell ligands and multiple receptor molecules present on the engulfing cell surface. This review concentrates on the molecular interactions operating in mammalian and non-mammalian systems for apoptotic cell recognition, as well as on the consequences of their signaling. Furthermore, some cellular models where the exposure of the phosphatidylserine (PS) phospholipid, a classical hallmark of the apoptotic phenotype, is not followed by cell death will be discussed.

Animals↗
PubMed2003

Laboratory and field validation of multiple molecular biomarkers of contaminant exposure in rainbow trout (Oncorhynchus mykiss).

Novel primers for three different genes (CYP1A1, vitellogenin, and metallothionein) for use in reverse transcription-polymerase chain reaction (RT-PCR) were developed and tested in laboratory flow-through experiments using model compounds benzo[a]pyrene, estradiol, and cadmium. Field validations of the molecular biomarkers were performed using 8-d or 48-h in situ, cagedexposure of juvenile rainbow trout (Oncorhynchus mykiss). Expression levels of genetranscription(messengerRNA [mRNA]) were monitored in gill and liver tissue after exposure at sites downstream of a known source of creosote contamination in the Little Scioto River (Marion, OH, USA) and metals and hydrocarbon contamination in Dick's Creek (Middletown, OH, USA). Significant increases of liver cytochrome P4501A1 gene (CYP1A1) and vitellogenin were measured in both streams at sites downstream of contaminant sources. Significant increases of gill CYP1A1 were also observed. Significant increases of gill and livermetallothionein occurred in Dick's Creek. A sample of gill tissue taken from each fish prior to placement in the Little Scioto River provided a pre-exposure control measurement for each individual. Expression of CYP1A1 and vitellogenin in trout at both streams indicated that exposure to bioavailable hydrocarbons and endocrine-disrupting compounds had taken place. Previous to this study, estrogenic compounds had not been detected in the Little Scioto River. Metallothionein expression confirmed the presence of metals in Dick's Creek. These results suggest a mixed contaminant environment that poses physiological hazard to existing teleost populations. Multiple molecular biomarkers provided a sensitive, physiologically based method of determining contaminant presence and bioavailability to aquatic organisms.

Animals↗
PubMed2004

Polycyclic aromatic hydrocarbons, environmental tobacco smoke, and respiratory symptoms in an inner-city birth cohort.

STUDY OBJECTIVES: Several studies have found associations between diesel exposure, respiratory symptoms, and/or impaired pulmonary function. We hypothesized that prenatal exposure to airborne polycyclic aromatic hydrocarbons (PAH), important components of diesel exhaust and other combustion sources, may be associated with respiratory symptoms in young children. We also hypothesized that exposure to environmental tobacco smoke (ETS) may worsen symptoms beyond that observed to be associated with PAH alone. DESIGN/PARTICIPANTS: To test our hypotheses, we recruited 303 pregnant women from northern Manhattan believed to be at high risk for exposure to both PAH and ETS, collected 48-h personal PAH exposure measurements, and monitored their children prospectively. RESULTS: By 12 months of age, more cough and wheeze were reported in children exposed to prenatal PAH in concert with ETS postnatally (PAH x ETS interaction odds ratios [ORs], 1.41 [p < 0.01] and 1.29 [p < 0.05], respectively). By 24 months, difficulty breathing and probable asthma were reported more frequently among children exposed to prenatal PAH and ETS postnatally (PAH x ETS ORs, 1.54 and 1.64, respectively [p < 0.05]). CONCLUSIONS: Our results suggest that early exposure to airborne PAH and ETS can lead to increased respiratory symptoms and probable asthma by age 12 to 24 months. Interventions to lower the risk of respiratory disease in young children living in the inner city may need to address the importance of multiple environmental exposures.

Adult↗
PubMedDate not supplied

Pregnancy with prolonged fetal exposure to an angiotensin-converting enzyme inhibitor.

Maternal exposure to angiotensin-converting enzyme (ACE) inhibitors has consistently been associated with significant fetal toxicity. We report the case of a 24-year-old woman, gravida 3, para 1-0-1-1 who presented at 24 2/7 weeks' gestation with initial abnormal fetal sonographic findings, including severe oligohydramnios, misshapen cranium, pericardial effusion, small bladder, and echogenic bowel, all after prolonged exposure to multiple medications including an ACE inhibitor. Eighteen days after discontinuation of the ACE inhibitor, repeat fetal sonography revealed normal amniotic fluid and normal cranial and fetal anatomy. The patient gave birth to a normal infant at 36 weeks' gestation. Poor neonatal outcome with prolonged antenatal exposure to ACE inhibitors is not inevitable. Early follow up sonographic evaluation in patients with prolonged exposure to ACE inhibitors may allow physicians to more accurately counsel patients on pregnancy outcome.

Adult↗
PubMed2001

Use of a pharmacokinetic model to assess chlorpyrifos exposure and dose in children, based on urinary biomarker measurements.

Chlorpyrifos is a common agricultural insecticide and has been used residentially in the United States until the year 2000 when this use was restricted by the U.S. Environmental Protection Agency (U.S. EPA). A chlorpyrifos metabolite, 3,5,6-trichloro-2-pyridinol (TCPy) has been found in urine samples collected during exposure field studies. In this work, we use urinary biomarker data and the inverse solution of a simple pharmacokinetic (PK) model for chlorpyrifos to estimate the magnitude and timing of doses. Three urine samples were collected on separate days from each of 15 children (ages 3-12) who were participants in the Minnesota Children's Pesticide Exposure Study (MNCPES). The total volume of urine was noted and samples analyzed for TCPY: The urinary data was used along with constraints imposed on dose timing, based on responses of the individuals to pesticide-use surveys. We predicted the time and magnitude of multiple "event" exposures characterized by short-term, relatively high doses superimposed over a continuous background exposure. The average dose of chlorpyrifos predicted by the model was 1.61 microg/kg per reported event. Average background dose rate for these children that reported exposure events was 0.0062 microg/kg/h, or 0.15 microg/kg/day. In addition to predicting the total dose of chlorpyrifos received by an individual from urinary biomarker measurements, the model can then be run in a forward manner once the exposure regime is determined. This will allow the prediction of the total amount of TCPy eliminated in the urine over any time period of interest.

Biomarkers↗
PubMedDate not supplied

[Environmental chemical pollution and toxic risk for humans: the particular role of organochlorine pesticides].

There is an increasing concern about environmental exposure to multiple chemicals and adverse changes in reproductive development, function, or behaviour in wildlife. The major group of environmental chemicals, such as organochlorine pesticides, polychlorinated biphenyls (PCBs) and other xenoestrogens are currently known to have estrogenic effects in vertebrates or fishes. Recent studies suggest that past exposure to such estrogenic compounds may affects the risk of developing breast cancer, precocious puberty, or impaired fertility in man.

Animals↗
PubMed2004

The role of topotecan for extending the platinum-free interval in recurrent ovarian cancer: an in vitro model.

OBJECTIVE: Topotecan, a novel topoisomerase-I inhibitor, is an active agent of second-line chemotherapy for extending the platinum-free interval (PFI) and improving the chances of a response to platinum in recurrent ovarian cancer patients. The aim of this study was to understand the molecular mechanism of topotecan-based second-line chemotherapy through an in vitro cell culture model and to gain clinical insight into sequencing issues for second-line treatment with novel agents versus retreatment with platinum. STUDY DESIGN: The human ovarian cancer cell line A2780 and the cisplatin resistance cell line A2780-CR were separately seeded in 6-well cell culture plates and then exposed to multiple concentrations of cisplatin plus paclitaxel or topotecan for 7 days. Surviving cells were recovered and cultured in drug-free media for 3 weeks and then replated in a 96-well microtiter plate. The LD(50) for these cells was determined by a cytotoxic MTT assay after exposure to multiple clinically relevant concentrations of cisplatin or topotecan. Surviving cells were cultured in drug-free media for an additional 4 weeks at which time the LD(50) was reassessed for each cell population by a second MTT assay. Using RT-PCR and Northern blot hybridization to measure mRNA expression, the molecular profile of these cells in terms of resistance was evaluated for the multidrug-resistant gene (MDR-1), multidrug-resistant protein (MRP), Topoisomerase-I, and beta-Actin. RESULTS: The LD(50) to cisplatin was unchanged in A2780-CR cells treated by topotecan. Those A2780-CR cells originally exposed to higher concentrations of cisplatin became more resistant to cisplatin in the MTT assays, while those A2780-CR cell lines treated with a combination of lower cisplatin concentrations and paclitaxel became more sensitive to cisplatin in the MTT assay (P < 0.01). The second MTT assay demonstrated that the LD(50) for cisplatin in every cell line decreased significantly after a 4-week drug-free interval (P < 0.01). There was no difference in the mRNA expression for MRP or topoisomerase-I regardless of cell line, or type or concentration of chemotherapeutic exposure. The mRNA for MDR-1 was uniquely overexpressed in the cisplatin-resistant cell line A2780-CR9 initially treated with low doses of cisplatin and paclitaxel, but was not amplified in A2780 (P < 0.01). CONCLUSIONS: The acquired resistance to cisplatin in A2780 is potentially due to P-glycoprotein-mediated multidrug resistance. This acquired resistance to cisplatin is an unstable phenotype in that some cell populations become sensitive after a drug-free interval and topotecan treatment. This reversal of resistance, however, does not appear to be simply due to loss of MDR-1 expression. While in vivo confirmation is required, agents with novel mechanisms of action offer a strategy to extend the platinum-free interval and thereby improve survival in patients with recurrent ovarian cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Biochemical reaction network modeling: predicting metabolism of organic chemical mixtures.

All organisms are exposed to multiple xenobiotics, through food, environmental contamination, and drugs. These xenobiotics often undergo biotransformation, a complex process that plays a critical role in xenobiotic elimination or bioactivation to toxic metabolites. Here we describe the results of a new computer-based simulation tool that predicts metabolites from exposure to multiple chemicals and interconnects their metabolic pathways, using four common drinking water pollutants (trichloroethylene, perchloroethylene, methylchloroform, and chloroform) as a test case. The simulation tool interconnected the metabolic pathways for these compounds, predicted reactive intermediates, such as epoxides and acid chlorides, and uncovered points in the metabolic pathways where typical endogenous compounds, such as glutathione or carbon dioxide, are consumed or generated. Moreover, novel metabolites, not previously reported, were predicted via this methodology. Metabolite prediction is based on a reaction-mechanism-based methodology, which applies fundamental organic and enzyme chemistry. The tool can be used to (a) complement experimental studies of chemical mixtures, (b) aid in risk assessment, and (c) help understand the effects of complex chemical mixtures. Our results indicate that this tool is useful for predictive xenobiotic metabolomics, providing new and important insights into metabolites and the interrelationship between diverse chemicals that hitherto may have remained unnoticed.

Computer Simulation↗
PubMed1986

Genetic counseling for teratogen exposure.

A consecutive series of 200 patients referred for genetic counseling after teratogen exposure was evaluated. One hundred four patients (52%) had exposure to more than one potentially teratogenic agent. One-third of the patients had a positive family history for genetic disease and 10% were of advanced maternal age. Genetic counseling was altered for the majority of patients when all risk factors (age, family history, and multiple teratogen exposure) were considered. Failure to evaluate all aspects of potential risk results in incomplete counseling. The majority of patients (97%) elected to continue their pregnancies after complete counseling. Three of five pregnancy terminations resulted from exposure to documented human teratogens. Precise risk assessment for the teratogen-exposed patient requires thorough genetic counseling to maximize successful pregnancy outcome.

Abnormalities, Drug-Induced↗
PubMed1996

Inhaled misoprostol blocks guinea pig antigen-induced bronchoconstriction and airway inflammation.

Inhaled E-type prostaglandins (PGE) have been shown to modulate responses to both allergic and nonallergic provocation. Misoprostol, a PGE1 analog, was developed as an antiulcer agent because it prevents gastrointestinal ulceration. Little is known about the effect inhaled misoprostol has on the airway and whether its potential antiasthmatic activity would be similar to other PGEs. Nebulizied solutions of misoprostol and PGE2 effectively blocked the acute bronchospasm caused by a subsequent inhaled antigen challenge in actively sensitized guinea pigs. The minimal concentration to result in a significant reduction in specific airway resistance was 3 and 30 micrograms/ml for misoprostol and PGE2, respectively. Exposure to a 300 micrograms/ml nebulized misoprostol solution provided significant protection for 2 h. Eosinophil recovery in bronchoalveolar lavage performed 24 h after antigen challenge was significantly reduced by 72%. In a chronic model of antigen-induced airway inflammation in which guinea pigs are given multiple antigen exposures over a 3-wk period, both misoprostol and its free acid-active metabolite 5C-30695 significantly reduced bronchoalveolar lavage eosinophils by 50 to 55%. Treatment with TRFK5, a monoclonal antibody to interleukin-5, resulted in a 76% decrease in eosinophil recovery. The combination of antibronchoconstrictive and anti-inflammatory effects suggests that inhaled misoprostol may be an effective treatment for the acute and chronic symptoms of asthma.

Administration, Inhalation↗
PubMedDate not supplied

Problems encountered in the design of epidemiologic studies of cancer in pesticide users.

Epidemiologic studies of cancer in pesticide users suffer from three main difficulties: lack of appropriate controls, exposure ascertainment, and exposure to multiple pesticides. Principles of control selection are discussed in the context of cohort and case-control studies. Residence on a farm is associated with unique dietary and lifestyle factors which are important to account for in case-control studies of pesticides users on farms. Exposure ascertainment methods include information collected from job descriptions, interviews, pesticide suppliers, expert panels, application records, passive dosimetry, and biological monitoring. Sensitive methods based on cell receptor-pesticide complexes have been proposed, but have not yet been validated and field tested as methods of quantitative exposure assessment. Examination of studies which successfully helped demonstrate cancer causation is suggested as a means of determining which epidemiologic methods are most fruitful and efficient at identifying human carcinogens.

Agricultural Workers' Diseases↗