Cocaine and opioid co-use is a notable public health concern, but little is known about correlates of this behavior. Most prior findings come from treatment samples and concern cocaine and heroin. Findings from a nationally representative... more
Cocaine and opioid co-use is a notable public health concern, but little is known about correlates of this behavior. Most prior findings come from treatment samples and concern cocaine and heroin. Findings from a nationally representative sample involving primarily prescription opioid misuse would expand knowledge. Past-12-month cocaine and/or opioid users in Wave 1 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) formed the sample (N = 839). Cocaine-only, opioid-only, and cocaine/opioid co-users were compared regarding sociodemographics, other substance involvement, psychiatric, and medical conditions/events. Opioid-only users were the largest group (n = 622), followed by cocaine-only (n = 144) and co-users (n = 73). The vast majority of opioid misuse was of prescription opioids (1.4% with past-12-month use of heroin). Notably, co-users did not differ from single drug users in frequency of use of either drug. Co-users did not have significantly greate...
Research Interests: Psychology, Comorbidity, Humans, Female, Male, and 4 morePrevalence, Adult, Substance use and misuse, and Health surveys
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Research Interests: Addiction, Psychometrics, Consumption, Adolescent, Family history, and 19 moreHumans, Substance Abuse, Alcoholism, Female, Alcohol Drinking, Male, Regression Analysis, Drug Addiction, Young Adult, Risk factors, Alcohol dependence, Binge drinking, Alcohol Abuse, Reproducibility of Results, Risk Factors, Wald test, Hybrid Model, Age of Onset, and Psychiatric Status Rating Scales
This study was designed to identify safety knowledge questions that differentiated those with high and low vulnerability to injury and assess differences in safety questions by sex and age. Colorado farm operators and their spouses were... more
This study was designed to identify safety knowledge questions that differentiated those with high and low vulnerability to injury and assess differences in safety questions by sex and age. Colorado farm operators and their spouses were recruited in 1993 from farm truck registrations (n = 872) and between 1993 and 1997 from property value assessment lists or rural directories (n = 761). Item Response Theory was used to assess ten safety questions. Knowing fatigue causes injury best discriminated between high and low injury vulnerability; incorrectly answering the question about inattention causing injury was associated with highest vulnerability to injury. No measurement invariance was identified by sex, but those older than 65 years answered differently than those younger than 45 years (P = 0.005). Safety programs emphasizing the role of fatigue and inattention on injury risk might reduce injuries in the farming community.
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Psychiatry and psychology are beginning to recognize the importance of lead, mercury and heavy metals as causal partners in the development of mental disorders. Further, mental health researchers and clinicians are embracing the idea that... more
Psychiatry and psychology are beginning to recognize the importance of lead, mercury and heavy metals as causal partners in the development of mental disorders. Further, mental health researchers and clinicians are embracing the idea that the combined effects of genetics and environmental exposures can result in perturbations in brain neurochemistry leading to psychiatric disorders. The purpose of this review is to examine the biological foundations for the epidemiological observations previously identified by reviewing the toxicology literature and relating it to epidemiological studies addressing the role of poisoning with organophosphate pesticides (OPs) in neurobehavioral and neuropsychological disorders. The goal of this review is to raise awareness in the mental health community about the possibility that affective disorders might be the result of contributions from environmental and occupational pesticide poisoning.
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To use structural equation modeling (SEM) to test the theory that a past pesticide poisoning may act as a mediator in the relationship between depression and safety practices. Depression has been associated with pesticide poisoning and... more
To use structural equation modeling (SEM) to test the theory that a past pesticide poisoning may act as a mediator in the relationship between depression and safety practices. Depression has been associated with pesticide poisoning and was more strongly associated with safety behaviors than workload, social support or health status of farm residents in a previously published report. A cross-sectional survey of farmers and their spouses was conducted in eight counties in northeastern Colorado. Depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression (CES-D) scale. Exploratory and confirmatory factor analyses were used to identify symptoms most correlated with risk factors for depression and safety practices. SEM was used to examine theoretical causal models of the relationship between depression and poor health, financial difficulties, a history of pesticide poisoning, and safety practices. Exploratory factor analysis identified three factors in the CES-D scale. The SEM showed that poor health, financial difficulties and a history of pesticide poisoning significantly explained the depressive symptoms. Models with an excellent fit for the safety behaviors resulted when modeling the probability that the pesticide poisoning preceded depression, but no fit was possible when reversing the direction and modeling depression preceding pesticide poisoning. Specific depressive symptoms appeared to be significantly associated with primarily animal handling and farm machinery. The order of events, based on SEM results, was a pesticide poisoning preceding depressed mood in relation to safety behaviors.
Research Interests: Health Behavior, Pain, Occupational Health, Depression, Social Support, and 22 moreSafety, Humans, Pesticides, Female, Male, Exploratory Factor Analysis, Risk factors, Structural Equation Model, Health Status, Colorado, Aged, Middle Aged, Public Administration and Policy, Adult, Cross Section, Public health systems and services research, Risk Factors, Depressive Symptoms, Cross Sectional Studies, Epidemiologic Studies, Causal Models, and Agromedicine
Manganese (Mn) inhalation has been associated with neuropsychological and neurological sequelae in exposed workers. Few environmental epidemiologic studies have examined the potentially neurotoxic effects of Mn exposure in ambient air on... more
Manganese (Mn) inhalation has been associated with neuropsychological and neurological sequelae in exposed workers. Few environmental epidemiologic studies have examined the potentially neurotoxic effects of Mn exposure in ambient air on motor function and hand tremor in adult community residents. Mn exposed residents were recruited in two Ohio towns: Marietta, a town near a ferro-manganese smelter, and East Liverpool, a town adjacent to a facility processing, crushing, screening, and packaging Mn products. Chronic (≥10years) exposure to ambient air Mn in adult residents and effects on neuropsychological and neurological outcomes were investigated. Participants from Marietta (n=100) and East Liverpool (n=86) were combined for analyses. AERMOD dispersion modeling of fixed-site outdoor air monitoring data estimated Mn inhalation over a ten year period. Adult Mn-exposed residents' psychomotor ability was assessed using Finger Tapping, Hand Dynamometer, Grooved Pegboard, and the Com...
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Several studies have suggested that high-level occupational exposure to pesticides may lead to depression, anxiety and other psychiatric illness, but few studies have examined lower-level environmental exposures and depression. We... more
Several studies have suggested that high-level occupational exposure to pesticides may lead to depression, anxiety and other psychiatric illness, but few studies have examined lower-level environmental exposures and depression. We analyzed data from 1,381 adults aged 20 years and older who participated in the 20052006 cycle of the National Health and Nutrition Examination Survey (NHANES) and had complete data on pesticide exposure and depression. Depression was assessed by the Patient Health Questionnaire-9 (PHQ-9) and analyzed as an ordinal outcome: not depressed (score 04), mildly depressed (score 59) and moderately/severely depressed (score 10+). Urinary pesticide levels (2,5-dichlorophenol, O-phenyl phenol, 2,4-dichlorophenol, 2,4,5-trichlorophenol, 2,4,6-trichlorophenol), primarily reflective of herbicide and fungicide exposure, were examined as categorical variables based on quartiles (or 50th and 75th percentile, depending on variability) of the distribution of exposure in th...
Manganese (Mn), an essential element, can be neurotoxic in high doses. This cross-sectional study explored the cognitive function of adults residing in two towns (Marietta and East Liverpool, Ohio, USA) that were identified as having high... more
Manganese (Mn), an essential element, can be neurotoxic in high doses. This cross-sectional study explored the cognitive function of adults residing in two towns (Marietta and East Liverpool, Ohio, USA) that were identified as having high levels of environmental airborne Mn from industrial sources. Air-Mn site surface emissions method modeling for total suspended particulate (TSP) ranged from 0.03 to 1.61μg/m(3) in Marietta and 0.01-6.32μg/m(3) in East Liverpool. A comprehensive screening test battery of cognitive function, including the domains of abstract thinking, attention/concentration, executive function and memory was administered. The mean age of the participants was 56 years (±10.8 years). Participants were mostly female (59%) and primarily white (94.6%). Significant relationships (p<0.05) were found between Mn exposure and performance on working and visuospatial memory (e.g., Rey-O Immediate β=-0.19, Rey-O Delayed β=-0.16) and verbal skills (e.g., Similarities β=-0.19). Using extensive cognitive testing and computer modeling of 10-plus years of measured air monitoring data, this study suggests that long-term environmental exposure to high levels of air Mn, the exposure metric of this paper, may result in mild deficits of cognitive function in adult populations.
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Research Interests: Risk, Humans, Female, Aged, Middle Aged, and 6 moreBiomarker, Estrogens, Adult, Biological markers, COMT, and Biochemistry and cell biology
This is the first study to examine the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), criteria for alcohol-use disorders and heavy episodic (or "binge") drinking in a college sample using... more
This is the first study to examine the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), criteria for alcohol-use disorders and heavy episodic (or "binge") drinking in a college sample using item-response theory (IRT) analysis. IRT facilitates assessment of the severity of the criteria, their ability to distinguish between those at greatest and lowest risk, and the value of adding a "binge" drinking criterion. In a sample of undergraduate drinkers (n = 353), we conducted factor analyses to determine whether the criteria best fit a one- or two-factor structure. We then conducted IRT analyses to obtain item-characteristic curves indicating the probability of endorsing a criterion at increasing levels of alcohol-use-disorder risk. These analyses were first conducted including current (i.e., past-year) DSM-IV alcohol-use-disorder criteria only and then rerun adding weekly "binge" drinking. A single-factor model of the DSM-IV cr...
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Research Interests: Child Development, Developing Countries, Agriculture, Risk assessment, Adolescent, and 21 moreNeurotoxicology, Pregnancy, Humans, Child, Toxicity, Text, Pesticides, Female, Male, Young Adult, Mental Disorders, Risk factors, Adult, Occupational Exposure, Time Factors, Age Factors, Risk Factors, Risk Assessment, Nervous System, Neurosciences, and Maternal Exposure
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To use structural equation modeling (SEM) to test the theory that a past pesticide poisoning may act as a mediator in the relationship between depression and safety practices. Depression has been associated with pesticide poisoning and... more
To use structural equation modeling (SEM) to test the theory that a past pesticide poisoning may act as a mediator in the relationship between depression and safety practices. Depression has been associated with pesticide poisoning and was more strongly associated with safety behaviors than workload, social support or health status of farm residents in a previously published report. A cross-sectional survey of farmers and their spouses was conducted in eight counties in northeastern Colorado. Depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression (CES-D) scale. Exploratory and confirmatory factor analyses were used to identify symptoms most correlated with risk factors for depression and safety practices. SEM was used to examine theoretical causal models of the relationship between depression and poor health, financial difficulties, a history of pesticide poisoning, and safety practices. Exploratory factor analysis identified three factors in the CES-D scale. The SEM showed that poor health, financial difficulties and a history of pesticide poisoning significantly explained the depressive symptoms. Models with an excellent fit for the safety behaviors resulted when modeling the probability that the pesticide poisoning preceded depression, but no fit was possible when reversing the direction and modeling depression preceding pesticide poisoning. Specific depressive symptoms appeared to be significantly associated with primarily animal handling and farm machinery. The order of events, based on SEM results, was a pesticide poisoning preceding depressed mood in relation to safety behaviors.
Research Interests: Health Behavior, Occupational Health, Depression, Social Support, Safety, and 21 moreHumans, Pesticides, Female, Male, Exploratory Factor Analysis, Risk factors, Structural Equation Model, Health Status, Colorado, Aged, Middle Aged, Public Administration and Policy, Adult, Cross Section, Public health systems and services research, Risk Factors, Depressive Symptoms, Cross Sectional Studies, Epidemiologic Studies, Causal Models, and Agromedicine
Respiratory hazards significantly contribute to the burden of occupational disease among farmers. Pesticide exposure has been linked to an increased prevalence of respiratory symptoms in several farming populations. The purpose of this... more
Respiratory hazards significantly contribute to the burden of occupational disease among farmers. Pesticide exposure has been linked to an increased prevalence of respiratory symptoms in several farming populations. The purpose of this study was to evaluate the association between respiratory symptoms and pesticide poisoning in a cross-sectional survey of farm residents. A total of 761 farm operators and their spouses, representing 479 farms in northeastern Colorado, were recruited from 1993 to 1997. A personal interview asked whether the resident had experienced a pesticide poisoning and several respiratory conditions including cough, allergy, wheeze, and organic dust toxic syndrome (ODTS). Spirometry testing was performed on 196 individuals. Logistic regression was used to model the association of pesticide poisoning with respiratory conditions, and linear regression was used to model the relationship of pesticide poisoning and forced vital capacity (FVC) and forced expiratory volume (FEV1). In unadjusted models, pesticide poisoning was associated with all four respiratory conditions, and stayed significant in adjusted models of allergies and cough in non-smokers. In age- and gender-adjusted models, pesticide poisoning was significantly associated with lower FVC and FEV1 in current smokers and in those who were not heavy drinkers. Although this study should be reproduced in a larger sample, it suggests that further evaluation of the respiratory effects of pesticide exposure is warranted.
Research Interests: Agriculture, Humans, Pesticides, Female, Male, and 13 moreYoung Adult, Risk factors, Colorado, Middle Aged, Spirometry, Adult, Vital Capacity, Occupational Exposure, Public health systems and services research, Risk Factors, Agricultural Safety and Health, Cross Sectional Studies, and Logistic Models
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Well-differentiated thyroid cancer most frequently occurs in premenopausal women. Greater exposure to estrogens may be a risk factor for thyroid cancer. To investigate the role of estrogens in thyroid cancer, a spot urine sample was... more
Well-differentiated thyroid cancer most frequently occurs in premenopausal women. Greater exposure to estrogens may be a risk factor for thyroid cancer. To investigate the role of estrogens in thyroid cancer, a spot urine sample was obtained from 40 women with thyroid cancer and 40 age-matched controls. Thirty-eight estrogen metabolites, conjugates and DNA adducts were analyzed by using ultraperformance liquid chromatography/tandem mass spectrometry and the ratio of adducts to metabolites and conjugates was calculated for each sample. The ratio of depurinating estrogen-DNA adducts to estrogen metabolites and conjugates significantly differed between cases and controls (p < 0.0001), demonstrating high specificity and sensitivity. These findings indicate that estrogen metabolism is unbalanced in thyroid cancer and suggest that formation of estrogen-DNA adducts might play a role in the initiation of thyroid cancer.
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Research Interests: Program Evaluation, Health Promotion, Leadership, Health Education, Adolescent, and 13 moreFaculty, Humans, Child, United States, Female, Male, Exercise, School nursing, Intervention Studies, School health services, Public health systems and services research, Curriculum and Pedagogy, and Pediatric Obesity
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Research Interests: Pharmacology, Bioinformatics, Evolutionary Biology, Pathology, Oncology, and 22 moreRadiology, Pharmacy, Informatics, Genomics, Phylogenetics, Computational Biology, Biotechnology, Cancer, Biomarkers, Biology, Proteomics, Biomedical informatics, Medicine, Bioscience, Phylogeny, Scientific, Microarray, Clinical Medicine, Biological, Genetic modification, Public health systems and services research, and Evidence Based
Research Interests: Addiction, Psychometrics, Consumption, Adolescent, Family history, and 19 moreHumans, Substance Abuse, Alcoholism, Female, Alcohol Drinking, Male, Regression Analysis, Drug Addiction, Young Adult, Risk factors, Alcohol dependence, Binge drinking, Alcohol Abuse, Reproducibility of Results, Risk Factors, Wald test, Hybrid Model, Age of Onset, and Psychiatric Status Rating Scales
The DSM-5 Substance-Related Disorders Work Group proposed to include Pathological Gambling within the current Substance-Related Disorders section. The objective of the current report was to assess four possible sets of diagnostic criteria... more
The DSM-5 Substance-Related Disorders Work Group proposed to include Pathological Gambling within the current Substance-Related Disorders section. The objective of the current report was to assess four possible sets of diagnostic criteria for Pathological Gambling. Gamblers (N=161) were defined as either Pathological or Non-Pathological according to four classification methods. (a) Option 1: the current DSM-IV criteria for Pathological Gambling; (b) Option 2: dropping the "Illegal Acts" criterion, while keeping the threshold at 5 required criteria endorsed; (c) Option 3: the proposed DSM-5 approach, i.e., deleting "Illegal Acts" and lowering the threshold of required criteria from 5 to 4; (d) Option 4: to use a set of Pathological Gambling criteria modeled on the DSM-IV Substance Dependence criteria. Cronbach's alpha and eigenvalues were calculated for reliability, Phi, discriminant function analyses, correlations and multivariate regression models were performed for validity and kappa coefficients were calculated for diagnostic consistency of each option. All criteria sets were reliable and valid. Some criteria had higher discriminant properties than others. The proposed DSM-5 criteria in Options 2 and 3 performed well and did not appear to alter the meanings of the diagnoses of Pathological Gambling from DSM-IV. Future work should further explore if Pathological Gambling might be assessed using the same criteria as those used for Substance Use Disorders.
Research Interests: Psychometrics, Item Response Theory, Adolescent, Humans, Substance Abuse, and 19 moreSubstance Use, Gambling, Female, Male, Heroin Dependence, Substance Dependence, Prescription drugs, Pathological Gambling, Middle Aged, Questionnaires, Adult, Empirical evidence, Reproducibility of Results, Street Drugs, Information Value, Substance-Related Disorders, Substance Use Disorder, Marijuana abuse, and Diagnostic Criteria
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Depressive symptoms have been associated with pesticide poisoning among farmers in cross-sectional studies, but no longitudinal studies have assessed the long-term influence of poisoning on depressive symptoms. The purpose of this study... more
Depressive symptoms have been associated with pesticide poisoning among farmers in cross-sectional studies, but no longitudinal studies have assessed the long-term influence of poisoning on depressive symptoms. The purpose of this study was to describe the associations between pesticide poisoning and depressive symptoms in a cohort of farm residents. Farm operators and their spouses were recruited in 1993 from farm truck registrations using stratified probability sampling. The Center for Epidemiologic Studies-Depression scale was used to evaluate depression in participants using generalized estimating equations. Baseline self-reported pesticide poisoning was the exposure of interest in longitudinal analyses. Pesticide poisoning was significantly associated with depression in three years of follow-up after adjusting for age, gender, and marital status (odds ratio [OR] 2.59; 95% confidence interval [CI] 1.20-5.58). Depression remained elevated after adjusting for health, decreased income, and increased debt (OR 2.00; CI 0.91-4.39) and was primarily due to significant associations with the symptoms being bothered by things (OR 3.29; CI 1.95-5.55) and feeling everything was an effort (OR 1.93; CI 1.14-3.27). Feeling bothered and that everything was an effort were persistently associated with a history of pesticide poisoning, supportive of the hypothesis that prolonged irritability may result from pesticide poisoning.
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Research Interests: Genetics, Computational Biology, Adolescent, Antisocial Personality Disorder, Humans, and 19 moreChild, Substance Abuse, Alcohol, Female, Male, Linkage, Genetic determinism, Genetic linkage analysis, Clinical Sciences, Middle Aged, Family Health, Adult, Antisocial Behavior, Genetic Mapping, Neurosciences, Substance-Related Disorders, Linkage Analysis, Substance Use Disorder, and genetic heterogeneity
Impaired control, defined as "a breakdown of an intention to limit... more
Impaired control, defined as "a breakdown of an intention to limit consumption" (Heather et al. J Stud Alcohol 1993; 54, 701), has historically been considered an important aspect of addiction. Despite recognition of its importance to addiction and potential value as an early indicator of problem drinking risk, we argue that impaired control over alcohol use has not received sufficient research attention. In an effort to spark further research, the present critical review offers brief discussion of the current state of knowledge regarding impaired control and avenues for future research. Three main research areas are addressed: (i) epidemiology; (ii) measurement issues; and (iii) potential mechanisms underlying relationships between impaired control and subsequent problem drinking. Measurement issues include complexities involved in self-report assessment of impaired control, development and validation of human and animal laboratory models, and impaired control's relationship to other constructs (i.e., impulsivity and other difficulties with self-control; symptoms of dependence such as craving). We discuss briefly 2 potential mechanisms that may help to explain why some drinkers experience impaired control while others do not: neurobiological dysfunction and family history/genetics. Suggestions for future research are focused on ways in which the impaired control construct may enhance prediction of who might be at particular risk of subsequent problem drinking and to facilitate intervention to reduce problem alcohol use.
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Research Interests: Psychology, Adolescent, Linear Model, Humans, United States, and 16 moreFemale, Male, Young Adult, Risk factors, Aged, Middle Aged, Adult, Dimensionality, Reproducibility of Results, Addictive Behaviors, Risk Factors, Drug Dependence, Substance Use Disorder, Marijuana abuse, Diagnostic Criteria, and Psychiatric Status Rating Scales
To examine the association between workload, health status, social support, depression, and safety practices among farm residents. Depression may lead to inattention when performing farm tasks and may reduce the likelihood of engaging in... more
To examine the association between workload, health status, social support, depression, and safety practices among farm residents. Depression may lead to inattention when performing farm tasks and may reduce the likelihood of engaging in safe practices. There is a paucity of studies examining factors that influence engaging in safety practices among farmers. Personal interviews were conducted with farm operators and spouses in an eight-county area in Colorado. The Center for Epidemiologic Studies-Depression (CES-D) scale was used to assess depression. Ten safety practices were assessed for those involved in farm work. Proportional odds and logistic regression were used to model the relationship between safety practices and modifiers of safety behavior. A total of 761 individuals were enrolled, of these 710 were actively involved in farm work. In logistic regression analysis, adjusting for age and gender, CES-D scale depression was significantly associated with being in a high-risk c...
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The purpose of the study presented is to evaluate the association between pesticides and depressive symptoms among a population exposed to chemicals as a result of agricultural use. Chronic sequelae of acute pesticide poisoning from... more
The purpose of the study presented is to evaluate the association between pesticides and depressive symptoms among a population exposed to chemicals as a result of agricultural use. Chronic sequelae of acute pesticide poisoning from organophosphate compounds may include anxiety and depression. In some states, farmers have been reported to have higher rates of depression than other population groups. Little work has been done to describe the effects of exposure to organophosphate compounds and depressive symptoms among the farming population. Data for this study came from a cross sectional survey of farmers and their spouses conducted in an eight county area in northeastern Colorado. Personal interviews were conducted with the study participants. Depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression (CES-D) scale. Pesticides applied on the farms were assessed using self-reported questionnaires. Conditional logistic regression was used to model the re...
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The role of pesticide poisoning in risk of injuries may operate through a link between pesticide-induced depressive symptoms and reduced engagement in safety behaviors. The authors conducted structural equation modeling of cross-sectional... more
The role of pesticide poisoning in risk of injuries may operate through a link between pesticide-induced depressive symptoms and reduced engagement in safety behaviors. The authors conducted structural equation modeling of cross-sectional data to examine the pattern of associations between pesticide poisoning, depressive symptoms, safety knowledge, safety behaviors, and injury. Interviews of 1637 Colorado farm operators and their spouses from 964 farms were conducted during 1993-1997. Pesticide poisoning was assessed based on a history of ever having been poisoned. The Center for Epidemiologic Studies-Depression scale was used to assess depressive symptoms. Safety knowledge and safety behaviors were assessed using ten items for each latent variable. Outcomes were safety behaviors and injuries. A total of 154 injuries occurred among 1604 individuals with complete data. Pesticide poisoning, financial problems, health, and age predicted negative affect/somatic depressive symptoms with similar effect sizes; sex did not. Depression was more strongly associated with safety behavior than was safety knowledge. Two safety behaviors were significantly associated with an increased risk of injury. This study emphasizes the importance of financial problems and health on depression, and provides further evidence for the link between neurological effects of past pesticide poisoning on risk-taking behaviors and injury.
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Research Interests: Nursing, Safety, Humans, Smoking, Pesticides, and 14 moreFemale, Male, Mental processes, Health Status, Colorado, Aged, Middle Aged, Adult, Occupational Exposure, Public health systems and services research, Logistic Models, Nervous System Diseases, Protective Clothing, and Occupational and environmental medicine
Research Interests: Nursing, Depression, Humans, Pesticides, North Carolina, and 14 moreFemale, Risk factors, Agrochemicals, Middle Aged, Occupational, Adult, Public health systems and services research, Odds ratio, Health surveys, Risk Factors, Iowa, Environmental Exposure, Case Control Studies, and Occupational and environmental medicine
Substantial evidence suggests that catechol estrogen-3,4-quinones react with DNA to form predominantly the depurinating adducts 4-hydroxyestrone (estradiol)-1-N3Ade [4-OHE(1)(E(2))-1-N3Ade] and 4-OHE(1)(E(2))-1-N7Gua. Apurinic sites... more
Substantial evidence suggests that catechol estrogen-3,4-quinones react with DNA to form predominantly the depurinating adducts 4-hydroxyestrone (estradiol)-1-N3Ade [4-OHE(1)(E(2))-1-N3Ade] and 4-OHE(1)(E(2))-1-N7Gua. Apurinic sites resulting from these adducts generate critical mutations that can initiate cancer. The paradigm of cancer initiation is based on an imbalance in estrogen metabolism between activating pathways that lead to estrogen-DNA adducts and deactivating pathways that lead to estrogen metabolites and conjugates. This imbalance can be improved to minimize formation of adducts by using antioxidants, such as resveratrol (Resv) and N-acetylcysteine (NAcCys). To compare the ability of Resv and NAcCys to block formation of estrogen-DNA adducts, we used the human breast epithelial cell line MCF-10F treated with 4-OHE(2). Resv and NAcCys directed the metabolism of 4-OHE(2) toward protective pathways. NAcCys reacted with the quinones and reduced the semiquinones to catechols. This pathway was also carried out by Resv. In addition, Resv induced the protective enzyme quinone reductase, which reduces E(1)(E(2))-3,4-quinones to 4-OHE(1)(E(2)). Resv was more effective at increasing the amount of 4-OCH(3)E(1)(E(2)) than NAcCys. Inhibition of estrogen-DNA adduct formation was similar at lower doses, but at higher doses Resv was about 50% more effective than NAcCys. Their combined effects were additive. Therefore, these two antioxidants provide an excellent combination to protect catechol estrogens from oxidation to catechol quinones.
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Research Interests: Agriculture, Multivariate Analysis, Biological Sciences, Insecticides, Environmental Sciences, and 18 moreHumans, Female, Male, Organophosphorus Compounds, CHEMICAL SCIENCES, Colorado, Aged, Middle Aged, Questionnaires, Adult, Occupational Exposure, Cross Section, Stepwise Regression, Cross Sectional Studies, Environmental, Logistic Models, Nervous System Diseases, and Confidence Interval
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Prior research has demonstrated the dimensionality of alcohol, nicotine and cannabis use disorders criteria. The purpose of this study was to examine the unidimensionality of DSM-IV cocaine, amphetamine and prescription drug abuse and... more
Prior research has demonstrated the dimensionality of alcohol, nicotine and cannabis use disorders criteria. The purpose of this study was to examine the unidimensionality of DSM-IV cocaine, amphetamine and prescription drug abuse and dependence criteria and to determine the impact of elimination of the legal problems criterion on the information value of the aggregate criteria. Factor analyses and Item Response Theory (IRT) analyses were used to explore the unidimensionality and psychometric properties of the illicit drug use criteria using a large representative sample of the U.S. population. All illicit drug abuse and dependence criteria formed unidimensional latent traits. For amphetamines, cocaine, sedatives, tranquilizers and opioids, IRT models fit better for models without legal problems criterion than models with legal problems criterion and there were no differences in the information value of the IRT models with and without the legal problems criterion, supporting the elimination of that criterion. Consistent with findings for alcohol, nicotine and cannabis, amphetamine, cocaine, sedative, tranquilizer and opioid abuse and dependence criteria reflect underlying unitary dimensions of severity. The legal problems criterion associated with each of these substance use disorders can be eliminated with no loss in informational value and an advantage of parsimony. Taken together, these findings support the changes to substance use disorder diagnoses recommended by the American Psychiatric Association's DSM-5 Substance and Related Disorders Workgroup.