Covalent protein adduction by drugs of abuse

Recreational abuse of the drugs cocaine, methamphetamine, and morphine continues to be prevalent in the United States of America and around the world. While numerous methods of detection exist for each drug, they are generally limited by the lifetime of the parent drug and its metabolites in the body. However, the covalent modification of endogenous proteins by these drugs of abuse may act as biomarkers of exposure and allow for extension of detection windows for these drugs beyond the lifetime of parent molecules or metabolites in the free fraction. Additionally, existence of covalently bound molecules arising from drug ingestion can offer insight into downstream toxicities associated with each of these drugs. This research investigated the metabolism of cocaine, methamphetamine, and morphine in common in vitro assay systems, specifically focusing on the generation of reactive intermediates and metabolites that have the potential to form covalent protein adducts. Results demonstrated the formation of covalent adduction products between biological cysteine thiols and reactive moieties on cocaine and morphine metabolites. Rigorous mass spectrometric analysis in conjunction with in vitro metabolic activation, pharmacogenetic reaction phenotyping, and computational modeling were utilized to characterize structures and mechanisms of formation for each resultant thiol adduction product. For cocaine, data collected demonstrated the formation of adduction products from a reactive arene epoxide intermediate, designating a novel metabolic pathway for cocaine. In the case of morphine, data expanded on known adduct-forming pathways using sensitive and selective analysis techniques, following the known reactive metabolite, morphinone, and a proposed novel metabolite, morphine quinone methide. Data collected in this study describe novel metabolic events for multiple important drugs of abuse, culminating in detection methods and mechanistic descriptors useful to both medical and forensic investigators when examining the toxicology associated with cocaine, methamphetamine, and morphine.

Patriarchal ideology and frequency of partner abuse among men in batterer treatment groups

This research examined the relative influence of a number of factors, patriarchal ideology, age, socio-economic status, partner relationship, and problem behaviors on the frequency of partner abuse. Patriarchal ideology as measured by the Attitudes Toward Women Scale (AWS), and the Inventory of Beliefs about Wife Beating (IBWB) among men in batterer treatment programs did not have the strong influence expected on whether men in treatment are more frequent abusers of their partners. Instead, having a criminal record and having been identified as having a substance abuse problem stood out as being the most influential factors associated with frequent partner abuse. Questionnaires were administered to 283 men in batterer treatment programs in Dade County Florida who volunteered to participate in the study. Specifically, men in batterer groups who scored low on the AWS or high on the IBWB indicating an adherence to patriarchal ideology were predicted to report more frequent abuse of their partners. Conversely, men in treatment who scored high on the AWS or low on the IBWB indicating a tendency towards a non-patriarchal ideology were predicted to report less frequent abuse. ^

Covalent Protein Adduction by Drugs of Abuse

Recreational abuse of the drugs cocaine, methamphetamine, and morphine continues to be prevalent in the United States of America and around the world. While numerous methods of detection exist for each drug, they are generally limited by the lifetime of the parent drug and its metabolites in the body. However, the covalent modification of endogenous proteins by these drugs of abuse may act as biomarkers of exposure and allow for extension of detection windows for these drugs beyond the lifetime of parent molecules or metabolites in the free fraction. Additionally, existence of covalently bound molecules arising from drug ingestion can offer insight into downstream toxicities associated with each of these drugs. This research investigated the metabolism of cocaine, methamphetamine, and morphine in common in vitro assay systems, specifically focusing on the generation of reactive intermediates and metabolites that have the potential to form covalent protein adducts. Results demonstrated the formation of covalent adduction products between biological cysteine thiols and reactive moieties on cocaine and morphine metabolites. Rigorous mass spectrometric analysis in conjunction with in vitro metabolic activation, pharmacogenetic reaction phenotyping, and computational modeling were utilized to characterize structures and mechanisms of formation for each resultant thiol adduction product. For cocaine, data collected demonstrated the formation of adduction products from a reactive arene epoxide intermediate, designating a novel metabolic pathway for cocaine. In the case of morphine, data expanded on known adduct-forming pathways using sensitive and selective analysis techniques, following the known reactive metabolite, morphinone, and a proposed novel metabolite, morphine quinone methide. Data collected in this study describe novel metabolic events for multiple important drugs of abuse, culminating in detection methods and mechanistic descriptors useful to both medical and forensic investigators when examining the toxicology associated with cocaine, methamphetamine, and morphine.

Socioemotional outcomes of children sexually abused during early childhood

This study investigated the nature and impact of the sexual abuse of children ages birth through 6 years. The purpose was to enhance knowledge about this understudied population through examination of: (1) characteristics of the abuse; (2) socioemotional developmental outcomes of young victims; and (3) potential moderating effects of family dynamics. An ecological-developmental theoretical framework was applied. Secondary data analysis was conducted using data collected from the consortium Longitudinal Studies of Child Abuse and Neglect (LONGSCAN). A sample of 250 children was drawn from LONGSCAN data, including children who were sexually abused (n=125) and their nonabused counterparts (n=125), matched on demographic variables. Results revealed that young victims of sexual abuse were disproportionately female (91 girls; 73%). The sexual abuse committed against these youngsters was severe in nature, with 111 children (89%) experiencing contact offenses ranging from fondling to forcible rape. Sixty-two percent of child victims demonstrated borderline, clinical, or less than adequate functioning on normative, expected socioemotional outcomes. Child victims reported low degrees of perceived competence and satisfaction in the social environment. When compared with their nonabused counterparts, child victims demonstrated significantly poorer socioemotional functioning, as evidenced by aggressive behaviors, attention and thought problems. Sexually abused youngsters also reported lower self-perceptions of cognitive and physical competence and maternal acceptance. Family dynamic factors did not significantly moderate the relationships between abuse and socioemotional outcomes, with one exception. The caregivers’ degree of empathy for their children had a significant moderating effect on the children’s social problems. This study contributes to an otherwise scant body of literature on the sexual abuse of preschoolers. Findings provide implications for social work practice, especially in the development of assessment and prevention strategies.

The effect of male -male competition and its underlying regulatory mechanisms on the electric signal of the gymnotiform fish Brachyhypopomus gauderio

Sexually-selected communication signals can be used by competing males to settle contests without incurring the costs of fighting. The ability to dynamically regulate the signal in a context-dependent manner can further minimize the costs of male aggressive interactions. Such is the case in the gymnotiform fish Brachyhypopomus gauderio, which, by coupling its electric organ discharge (EOD) waveform to endocrine systems with circadian, seasonal, and behavioral drivers, can regulate its signal to derive the greatest reproductive benefit. My dissertation research examined the functional role of the EOD plasticity observed in male B. gauderio and the physiological mechanisms that regulate the enhanced male EOD. To evaluate whether social competition drives the EOD changes observed during male-male interactions, I manipulated the number of males in breeding groups to create conditions that exemplified low and high competition and measured their EOD and steroid hormone levels. My results showed that social competition drives the enhancement of the EOD amplitude of male B. gauderio. In addition, changes in the EOD of males due to changes in their social environment were paralleled by changes in the levels of androgens and cortisol. I also examined the relationship between body size asymmetry, EOD waveform parameters, and aggressive physical behaviors during male-male interactions in B. gauderio, in order to understand more fully the role of EOD waveforms as reliable signals. While body size was the best determinant of dominance in male B. gauderio, EOD amplitude reliably predicted body condition, a composite of length and weight, for fish in good body condition. To further characterize the mechanisms underlying the relationship between male-male interactions and EOD plasticity, I identified the expression of the serotonin receptor 1A, a key player in the regulation of aggressive behavior, in the brains of B. gauderio. I also identified putative regulatory regions in this receptor in B. gauderio and other teleost fish, highlighting the presence of additional plasticity. In conclusion, male-male competition seems to be a strong selective driver in the evolution of the male EOD plasticity in B. gauderio via the regulatory control of steroid hormones and the serotonergic system.

Leaf Gas Exchange and Nutrient Use Efficiency Help Explain the Distribution of Two Neotropical Mangroves under Contrasting Flooding and Salinity

Rhizophora mangle and Laguncularia racemosa cooccur along many intertidal floodplains in the Neotropics. Their patterns of dominance shift along various gradients, coincident with salinity, soil fertility, and tidal flooding. We used leaf gas exchange metrics to investigate the strategies of these two species in mixed culture to simulate competition under different salinity concentrations and hydroperiods. Semidiurnal tidal and permanent flooding hydroperiods at two constant salinity regimes (10 g L−1 and 40 g L−1) were simulated over 10 months. Assimilation ( ), stomatal conductance ( ), intercellular CO2 concentration ( ), instantaneous photosynthetic water use efficiency (PWUE), and photosynthetic nitrogen use efficiency (PNUE) were determined at the leaf level for both species over two time periods. Rhizophora mangle had significantly higher PWUE than did L. racemosa seedlings at low salinities; however, L. racemosa had higher PNUE and and, accordingly, had greater intercellular CO2 (calculated) during measurements. Both species maintained similar capacities for A at 10 and 40 g L−1 salinity and during both permanent and tidal hydroperiod treatments. Hydroperiod alone had no detectable effect on leaf gas exchange. However, PWUE increased and PNUE decreased for both species at 40 g L−1 salinity compared to 10 g L−1. At 40 g L−1 salinity, PNUE was higher for L. racemosa than R. mangle with tidal flooding. These treatments indicated that salinity influences gas exchange efficiency, might affect how gases are apportioned intercellularly, and accentuates different strategies for distributing leaf nitrogen to photosynthesis for these two species while growing competitively.

Effects of invasive Africanized honey bees (Apis mellifera scutellata) on native stingless bee populations (Meliponinae) and traditional Mayan beekeeping in central Quintana Roo, Mexico

The Maya of the Yucatan region have a long history of keeping the native stingless bees (subfamily Meliponinae). However, market forces in the last few decades have driven the Maya to favor the use of invasive Africanized honey bees (Apis mellifera scutellata) for producing large quantities of high quality honey that has an international market. Furthermore, the native bees traditionally used by the Maya are now disappearing, along with the practice of keeping them. ^ An interdisciplinary approach was taken in order to determine the social factors behind the decrease in stingless beekeeping and the ecological driving forces behind their disappearance from the wild. Social research methods included participant observation with stingless beekeepers, Apis beekeepers, and marketing intermediaries. Ecological research methods included point observations of commonly known melliferous and polliniferous plants along transects in three communities with different degrees of human induced ecosystem disturbance. ^ The stingless bee species most important to the Maya, Melipona beecheii, has become extremely rare, and this has caused a breakdown of stingless beekeeping tradition, compounded with the pressure of the market economy, which fuels Apis beekeeping and has lessened the influence of traditional practices. The community with the heaviest amount of human induced ecosystem disturbance also had the highest degree of dominance of Apis mellifera, while the area with the most intact ecosystem had the highest diversity of stingless bees, though Apis mellifera was still the dominant species. Aggressive competitive behavior involving physical attacks by Apis mellifera against stingless bees was observed on several occasions, and this is a new observation previously unreported by science. ^

The Effect of male-male competition and its Underlying Regulatory Mechanisms on the Electric Signal of the Gymnotiform fish Brachyhypopomus gauderio

Sexually-selected communication signals can be used by competing males to settle contests without incurring the costs of fighting. The ability to dynamically regulate the signal in a context-dependent manner can further minimize the costs of male aggressive interactions. Such is the case in the gymnotiform fish Brachyhypopomus gauderio, which, by coupling its electric organ discharge (EOD) waveform to endocrine systems with circadian, seasonal, and behavioral drivers, can regulate its signal to derive the greatest reproductive benefit. My dissertation research examined the functional role of the EOD plasticity observed in male B. gauderio and the physiological mechanisms that regulate the enhanced male EOD. To evaluate whether social competition drives the EOD changes observed during male-male interactions, I manipulated the number of males in breeding groups to create conditions that exemplified low and high competition and measured their EOD and steroid hormone levels. My results showed that social competition drives the enhancement of the EOD amplitude of male B. gauderio. In addition, changes in the EOD of males due to changes in their social environment were paralleled by changes in the levels of androgens and cortisol. I also examined the relationship between body size asymmetry, EOD waveform parameters, and aggressive physical behaviors during male-male interactions in B. gauderio, in order to understand more fully the role of EOD waveforms as reliable signals. While body size was the best determinant of dominance in male B. gauderio, EOD amplitude reliably predicted body condition, a composite of length and weight, for fish in good body condition. To further characterize the mechanisms underlying the relationship between male-male interactions and EOD plasticity, I identified the expression of the serotonin receptor 1A, a key player in the regulation of aggressive behavior, in the brains of B. gauderio. I also identified putative regulatory regions in this receptor in B. gauderio and other teleost fish, highlighting the presence of additional plasticity. In conclusion, male-male competition seems to be a strong selective driver in the evolution of the male EOD plasticity in B. gauderio via the regulatory control of steroid hormones and the serotonergic system.

Socioemotional Outcomes of Children Sexually Abused during Early Childhood

This study investigated the nature and impact of the sexual abuse of children ages birth through 6 years. The purpose was to enhance knowledge about this understudied population through examination of: (1) characteristics of the abuse; (2) socioemotional developmental outcomes of young victims; and (3) potential moderating effects of family dynamics. An ecological-developmental theoretical framework was applied. Secondary data analysis was conducted using data collected from the consortium Longitudinal Studies of Child Abuse and Neglect (LONGSCAN). A sample of 250 children was drawn from LONGSCAN data, including children who were sexually abused (n=125) and their nonabused counterparts (n=125), matched on demographic variables. Results revealed that young victims of sexual abuse were disproportionately female (91 girls; 73%). The sexual abuse committed against these youngsters was severe in nature, with 111 children (89%) experiencing contact offenses ranging from fondling to forcible rape. Sixty-two percent of child victims demonstrated borderline, clinical, or less than adequate functioning on normative, expected socioemotional outcomes. Child victims reported low degrees of perceived competence and satisfaction in the social environment. When compared with their nonabused counterparts, child victims demonstrated significantly poorer socioemotional functioning, as evidenced by aggressive behaviors, attention and thought problems. Sexually abused youngsters also reported lower self-perceptions of cognitive and physical competence and maternal acceptance. Family dynamic factors did not significantly moderate the relationships between abuse and socioemotional outcomes, with one exception. The caregivers’ degree of empathy for their children had a significant moderating effect on the children’s social problems. This study contributes to an otherwise scant body of literature on the sexual abuse of preschoolers. Findings provide implications for social work practice, especially in the development of assessment and prevention strategies.

Implementing Employee Drug and Alcohol Testing: Implications for Hotel Managers

Abuse of drugs and alcohol in the workplace has reached epidemic proportions in the hotel industry. The authors review considerations for drug testing and discuss drug and alcohol testing methods and the manner in which an effective policy should be developed.

Reaching home : a novel

This is the coming-of-age story of a twelve-year-old girl who lives in a Florida fishing village in 1968, and is thought to be retarded. On a birthday trip to see dolphins perform at a road side show she learns that they are captives simply because man believes he has the right of dominance over "dumb" animals. This emotionally conquered child develops a feeling of kinship to these dolphins and when, with outside help, she discovers that she is dyslexic, not retarded, it frees her to recognize that errors in thinking may exist at many levels. Her release from the trap of human ignorance allows her to devise a way to free the dolphins and guide them home to the sea.

An evaluation of child welfare inservice training: The relative effectiveness of substance abuse content in improving worker knowledge and attitudes

Given the seriousness of substance abuse as a child welfare problem, the purpose of this study was to examine the relative effectiveness of an inservice training curriculum for child welfare workers. The training was designed to improve worker knowledge and attitudes in working with substance abusing families. Seventy (70) child welfare workers from public and private agencies in two south Florida counties participated in a pretest/posttest control group design that also trained and retested the control group. The literature review supports that the general preparedness of child welfare workers for the issues presented by substance abusing families is in question. Confounding this problem is a lack of understanding of substance abuse dynamics, worker biases, and predispositions. The two research hypotheses focused on whether inservice training could increase worker knowledge and improve worker attitudes in working with this population. Training delivery was in the form of a five-day inservice focusing on an array of substance abuse knowledge and attitudinal topics. Separate knowledge and attitude instruments were developed for the research and were administered, before and after training, to a purposive sample of participants that were randomly assigned to the experimental and control groups. The data analysis supported the research hypotheses but raised a question. Specifically, the experimental group demonstrated significant improvement in posttest scores on both instruments after receiving the training; whereas the control group, with training withheld, also demonstrated a significant improvement at posttest, but only on the knowledge instrument. Although the question was unanswered, when examined at a more critical significance level, only the experimental group remained significant. The hypotheses were reconfirmed when, after training and retesting, the control group also displayed significant improvement on both instruments. The findings support the conclusion that this substance abuse inservice was effective in improving worker knowledge and attitudes regarding working with substance abusing families. As an implication for social work practice, it suggests that similar inservice training can be a viable training resource when formal substance abuse training is unavailable. Additional research is suggested regarding to what degree increased substance abuse knowledge and improved worker attitudes correlate with improved practice.

Gender differences in behavioral and psychosocial correlates of substance abuse among adolescents in residential treatment

This dissertation reports the results of a study that examined differences between genders in a sample of adolescents from a residential substance abuse treatment facility. The sample included 72 males and 65 females, ages 12 through 17. The data were archival, having been originally collected for a study of elopement from treatment. The current study included 23 variables. The variables were from multiple dimensions, including socioeconomic, legal, school, family, substance abuse, psychological, social support, and treatment histories. Collectively, they provided information about problem behaviors and psychosocial problems that are correlates of adolescent substance abuse. The study hypothesized that these problem behaviors and psychosocial problems exist in different patterns and combinations between genders.^ Further, it expected that these patterns and combinations would constitute profiles important for treatment. K-means cluster analysis identified differential profiles between genders in all three areas: problem behaviors, psychosocial problems, and treatment profiles. In the dimension of problem behaviors, the predominantly female group was characterized as suicidal and destructive, while the predominantly male group was identified as aggressive and low achieving. In the dimension of psychosocial problems, the predominantly female group was characterized as abused depressives, while the male group was identified as asocial, low problem severity. A third group, neither predominantly female or male, was characterized as social, high problem severity. When these dimensions were combined to form treatment profiles, the predominantly female group was characterized as abused, self-harmful, and social, and the male group was identified as aggressive, destructive, low achieving, and asocial. Finally, logistic regression and discriminant analysis were used to determine whether a history of sexual and physical abuse impacted problem behavior differentially between genders. Sexual abuse had a substantially greater influence in producing self-mutilating and suicidal behavior among females than among males. Additionally, a model including sexual abuse, physical abuse, low family support, and low support from friends showed a moderate capacity to predict unusual harmful behavior (fire-starting and cruelty to animals) among males. Implications for social work practice, social work research, and systems science are discussed. ^

An evaluation of coping ability as a guide to the treatment of persons diagnosed with schizophrenia and substance abuse

This dissertation introduced substance abuse to the Dynamic Vulnerability Formulation (DVF) and the social competence model to determine if the relationship between schizophrenic symptomatology and coping ability in the DVF applied also to the dually diagnosed schizophrenic or if these variables needed to be modified. It compared the coping abilities of dually and singly diagnosed clients in day treatment and identified, examined, and assessed the relative influence of relevant mediating variables on two dimensions of coping ability of the dually diagnosed: coping skills and coping effort. These variables were: presence of negative and nonnegative symptoms, duration of mental illness, type of substance used, and age of first substance use.^ A priori effect sizes based on previous empirical research were used to interpret the results related to the comparison of demographic, socioeconomic, and treatment characteristics between the singly and dually diagnosed study samples. The data suggested that the singly diagnosed group had higher coping skills than the dually diagnosed group, particularly in the areas of housing stability, work affect, and total social adjustment. The dually diagnosed group had lower scores on one aspect of coping effort--agency or self-efficacy. The data supported the presence of an inverse relationship between symptom severity and coping skills, particularly for the dually diagnosed group. The data did not support the presence of an inverse relationship between symptom severity and coping effort, but did suggest a positive relationship between symptom severity and one measure of coping effort, agency, for the dually diagnosed group. Regression equations using each summary measure of coping skill--social adjustment and role functioning--yielded statistically significant F-ratios. Thirty-six percent of the variance in social adjustment and thirty-one percent of the variance in role functioning were explained by the relative influence of the relevant variables. Both negative and non-negative symptoms were the only significant predictors of social adjustment. The non-negative symptoms variable was the sole significant predictor of role functioning. The results of this study provided partial support for the use of the Dynamic Vulnerability Formulation (DVF) with the dually diagnosed. ^

A phenomenology of crack abuse

The aim of this dissertation is to identify, describe, and explain the common experiences defining the crack abuser's life-world. Its method is phenomenological. Using basic cybernetic premises, a neurophysiologically oriented phenomenological framework concerning the constitution of thoughts, memories, and perceptions is first written. The framework is designed to hypothetically represent the neuropathology of crack abuse within a perspective that prescinds and describes the constitution, flow, and interdependence of experience. After the framework is written, the dissertation outlines the neuro-psychopharmacology of crack abuse and delimits crack abusers as a specific group within the more general population of cocaine users. It then represents the neuropathology of crack abuse within its phenomenological framework and uses the first-person accounts of forty-two crack dependents to actualize a phenomenological sketch of the crack abuser's life-world. The ethnographies afford the possibility of writing a “thick” description of the crack abuser's daily life—one that communicates the substance, order, and subjective and cultural dimensions of the dependent's defining experiences. ^ The dissertation's goals are successfully realized. The framework written and the ethnographies recorded and transcribed, the dissertation is able to identify, describe, and to a certain extent explain some of the common experiences defining the crack abusers life-world. The dissertation concludes that the crack abuser's life-world is organized around three primary and four secondary experiences. His primary experiences include: (1) an almost complete, yet fleeting, satisfaction of the ego's innate insufficiency and sublime, erotic-like stimulation of its core, (2) a fundamental inclination and expansion of the uniquely oriented euphoria-dysphoria dynamic that vivifies and orients the flow of consciousness, and (3) a change in the ego's innate structure. His secondary experiences include: (a) a characteristic aiming of projects, actions, and conduct toward the procurement and consumption of crack, (b) a denigration in the hold of legitimations and institutionalizations on the thematic field, (c) a strict alignment and a contraction in the scope of logical types pointing to the salient experiences within the stock of knowledge, and (d) for some crack abusers, ontological insecurity, despair, and exhaustion. ^