Effects of the glucocorticoid antagonist, mifepristone, on the consequences of withdrawal from long term alcohol consumption

BACKGROUND: Studies were carried out to test the hypothesis that administration of a glucocorticoid Type II receptor antagonist, mifepristone (RU38486), just prior to withdrawal from chronic alcohol treatment, would prevent the consequences of the alcohol consumption and withdrawal in mice. MATERIALS AND METHODS: The effects of administration of a single intraperitoneal dose of mifepristone were examined on alcohol withdrawal hyperexcitability. Memory deficits during the abstinence phase were measured using repeat exposure to the elevated plus maze, the object recognition test, and the odor habituation/discrimination test. Neurotoxicity in the hippocampus and prefrontal cortex was examined using NeuN staining. RESULTS: Mifepristone reduced, though did not prevent, the behavioral hyperexcitability seen in TO strain mice during the acute phase of alcohol withdrawal (4 hours to 8 hours after cessation of alcohol consumption) following chronic alcohol treatment via liquid diet. There were no alterations in anxiety-related behavior in these mice at 1 week into withdrawal, as measured using the elevated plus maze. However, changes in behavior during a second exposure to the elevated plus maze 1 week later were significantly reduced by the administration of mifepristone prior to withdrawal, indicating a reduction in the memory deficits caused by the chronic alcohol treatment and withdrawal. The object recognition test and the odor habituation and discrimination test were then used to measure memory deficits in more detail, at between 1 and 2 weeks after alcohol withdrawal in C57/BL10 strain mice given alcohol chronically via the drinking fluid. A single dose of mifepristone given at the time of alcohol withdrawal significantly reduced the memory deficits in both tests. NeuN staining showed no evidence of neuronal loss in either prefrontal cortex or hippocampus after withdrawal from chronic alcohol treatment. CONCLUSIONS: The results suggest mifepristone may be of value in the treatment of alcoholics to reduce their cognitive deficits.

The use of treatment process variables to differentiate between completers and dropouts for a guided self -change adolescent substance abuse intervention

This study documented differences between substance using adolescent participants who either completed or dropped out of a brief motivational intervention. Therapeutic alliance, working alliance and patient involvement were used to describe differences in treatment process ratings in a sample of majority Latino males who either (a) completed a adolescent substance abuse intervention called Alcohol Treatment Targeting Adolescents In Need (ATTAIN) or (b) dropped out after the first or second Guided Self-Change therapy session. Fifteen-minute segments were copied from the midpoint of previously recorded audio-tapes of Guided Self-Change therapy sessions. Raters were trained to a criterion level of interrater reliability for both the Working Alliance Inventory-Short and Vanderbilt Psychotherapy Process Scale. Correlations among Working Alliance Inventory- Short and Vanderbilt Psychotherapy Process Scale subscales reflected a general similarity in the assignment of ratings to client-therapist dyads. Findings underscore why these concepts are often used interchangeably in the treatment process literature. The Vanderbilt Psychotherapy Process Scale patient participation subscale demonstrated substantial empirical differentiation from overall therapeutic alliance. Discriminant function analysis demonstrated the Working Alliance Inventory-Short goal subscale and the Vanderbilt Psychotherapy Process Scale patient participation and therapist warmth and friendliness subscales as successful classifiers of groups of mostly Latino youth based on completion status. Follow-up logistic regression analyses confirmed major findings and successfully predicted group membership. Treatment process constructs can be used as clinical tools to identify participants who may be susceptible to dropping out of treatment services. Further investigation of treatment process may enhance understanding of the influence of alliance between clients and Guided Self-Change therapists. Investigating the role of treatment process as a critical component of brief motivational interventions for substance-using adolescents will inform both practitioners and researchers regarding the effectiveness of community-based substance abuse interventions for adolescents.

Attachment Security and Alexithymia in a Heavy Drinking Population

Attachment difficulties have been proposed as a key risk factor for the development of alexithymia, a multifaceted personality trait characterised by difficulties identifying and describing feelings, a lack of imagination and an externally oriented thinking style. The present study investigated the relationship between attachment and alexithymia in an alcohol dependent population. Participants were 210 outpatients in a Cognitive Behavioural Treatment Program assessed on the Toronto Alexithymia Scale (TAS-20) and the Revised Adult Attachment Scale (RAAS). Significant relationships between anxious attachment and alexithymia factors were confirmed. Furthermore, alexithymic alcoholics reported significantly higher levels of anxious attachment and significantly lower levels of closeness (secure attachment) compared to non-alexithymic alcoholics. These findings highlight the importance of assessing and targeting anxious attachment among alexithymic alcoholics in order to improve alcohol treatment outcomes. Keywords: Attachment, alexithymia, alcohol dependence.

The formulation, testing and stability of 16% fat cream liqueurs

Cream liqueurs manufactured by a one-step process, where alcohol was added before homogenisation, were more stable than those processed by a two -step process which involved addition of alcohol after homogenisation. Using the one-step process, it was possible to produce creaming-stable liqueurs by using one pass through a homogeniser (27.6 MPa) equipped with "liquid whirl" valves. Test procedures to characterise cream liqueurs and to predict shelf life were studied in detail. A turbidity test proved simple, rapid and sensitive for characterising particle size and homogenisation efficiency. Prediction of age thickening/gelation in cream liqueurs during incubation at 45 °C depended on the age of the sample when incubated. Samples that gelled at 45 °C may not do so at ambient temperature. Commercial cream liqueurs were similar in gross chemical composition, and unlike experimentally produced liqueurs, these did not exhibit either age-gelation at ambient or elevated temperatures. Solutions of commercial sodium caseinates from different sources varied in their calcium sensitivity. When incorporated into cream liqueurs, caseinates influenced the rate of viscosity increase, coalescence and, possibly, gelation during incubated storage. Mild heat and alcohol treatment modified the properties of caseinate used to stabilise non-alcoholic emulsions, while the presence of alcohol in emulsions was important in preventing clustering of globules. The response to added trisodium citrate varied. In many cases, addition of the recommended level (0.18%) did not prevent gelation. Addition of small amounts of NaOH with 0.18 % trisodium citrate before homogenisation was beneficial. The stage at which citrate was added during processing was critical to the degree of viscosity increase (as opposed to gelation) in the product during 45 °C incubation. The component responsible for age-gelation was present in the milk-solids non fat portion of the cream and variations in the creams used were important in the age-gelation phenomenon Results indicated that, in addition to possibly Ca++, the micellar casein portion of serum may play a role in gelation. The role of the low molecular weight surfactants, sodium stearoyl lactylate and monodiglycerides in preventing gelation, was influenced by the presence of trisodium citrate. Clustering of fat globules and age-gelation were inhibited when 0.18 % citrate was included. Inclusion of sodium stearoyl lactylate, but not monodiglycerides, reduced the extent of viscosity increase at 45 °C in citrate containing liqueurs.

Alcoholism and coagulating gland: Androgen and insulin like growth factor-1 receptor features

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Morphologic changes in the vesical transition epithelium of alcoholic rats

Few studies are available about the effect of alcohol on the epithelium of the urinary bladder. In the present investigation we studied the ultrastructure of the vesical transition epithelium of normal rats and of rats submitted to experimental chronic alcoholism. Adult rats were submitted to experimental chronic alcoholism by the ingestion of sugar cane liquor. The vesical epithelium was examined after 60, 120, 180 and 240 days of alcohol treatment by transmission electron microscopy. Surface cells presented nuclear and cytoplasmic changes and marked cellular desquamation. There was an increase in multivesicular bodies and lysosomes suggesting cell degeneration. Mast cell infiltration was observed, possibly related to increased epithelial sensitivity. Intercellular spaces were frequently observed. The transition epithelium of the urinary bladder was found to be sensitive to the action of alcohol, as demonstrated by the changes in the components of the blood-urine barrier, the greater sensitivity to inflammation, the increase in cell desquamation and the greater recycling of the apical membrane and of the fusiform vesicles of surface cells observed in alcoholic rats.

Experimental alcoholism and pathogenesis of prostatic diseases in UChB rats

Previous studies have shown that long-term alcohol treatment has negative effects on prostatic stromal-epithelial interaction. Thus, the aim of the present study was to analyze the histochemical, immunohistochemical and ultrastructural alterations that occur in the prostatic stroma and epithelium of rats submitted to chronic alcohol ingestion and alcohol abstinence, as well as to establish the relationship between these changes and prostatic diseases. Thirty male rats (10 Wistar and 20 UChB rats) were divided into three experimental groups: the control group received tap water, the alcoholic group received ethanol diluted to 10 degrees G.L. for 150 days, and the abstinent group received the same liquid diet as the alcoholic group up to 120 days of treatment and only tap water for 30 days thereafter. At the end of treatment, all animals were sacrificed and the ventral lobe of the prostate was removed and processed for histochemical, immunohistochemical and ultrastructural analyses. In addition, plasma testosterone levels were measured. The results showed, prostatic intraepithelial neoplasia, infolding of the epithelium towards the stroma, stromal hypertrophy and the presence of inflammatory cells in alcoholic animals. In the abstinent group, alterations were noted mainly in the stromal area. In conclusion, ethanol triggers alterations in prostatic epithelial and stromal compartments, affecting the stromal microenvironment and predisposing the organ to pathological processes. (C) 2006 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.

Tratamento endurecedor para cones de guta-percha.

The subject of this work was to study a hardening procedure for gutta-percha points, in order to make ease their introduction in very curved root canals. Gutta-percha points of different brands and dimensions were submitted to treatment with alcohol 96 degrees for 1 to 3 days. After this treatment the weight necessary to make a bending of 35 degrees on the tip of the gutta-percha was evaluated. The obtained results were submitted to statistic analysis and the following conclusions can be observed: a. The treatment with alcohol make hard the gutta-percha points in a significant level. b. There was not significant differences between the results obtained with more than one day of alcohol treatment. c. The treatment with alcohol do not make hard all the brands of gutta-percha points.

Estudo da modificação ácido-etanólica do amido de mandioca seguida de moagem

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

A study of multiple mating habit in Atta laevigata based on the DNA content

1. 1. Pure DNA was isolated from the genital organs of the Atta laevigata by the sodium dodecylsulfate method and chloroform-isoamyl alcohol treatment. 2. 2. The DNA content in sexual cells of winged mature subjects gives a new method in the analysis of multiple mating in such species of ants. 3. 3. From the data we concluded that each queen had at least three mates during the nuptial flight. © 1981.

Different addictive drug exposure induces selective alterations of the Endogenous Opioid System : modulation of transcription and epigenetic mechanisms

Drug addiction manifests clinically as compulsive drug seeking, and cravings that can persist and recur even after extended periods of abstinence. The fundamental principle that unites addictive drugs is that each one enhances synaptic DA by means that dissociate it from normal behavioral control, so that they act to reinforce their own acquisition. Our attention has focused on the study of phenomena associated with the consumption of alcohol and heroin. Alcohol has long been considered an unspecific pharmacological agent, recent molecular pharmacology studies have shown that acts on different primary targets. Through gene expression studies conducted recently it has been shown that the classical opioid receptors are differently involved in the consumption of ethanol and, furthermore, the system nociceptin / NOP, included in the family of endogenous opioid system, and both appear able to play a key role in the initiation of alcohol use in rodents. What emerges is that manipulation of the opioid system, nociceptin, may be useful in the treatment of addictions and there are several evidences that support the use of this strategy. The linkage between gene expression alterations and epigenetic modulation in PDYN and PNOC promoters following alcohol treatment confirm the possible chromatin remodeling mechanism already proposed for alcoholism. In the second part of present study, we also investigated alterations in signaling molecules directly associated with MAPK pathway in a unique collection of postmortem brains from heroin abusers. The interest was focused on understanding the effects that prolonged exposure of heroin can cause in an individual, over the entire MAPK cascade and consequently on the transcription factor ELK1, which is regulated by this pathway. We have shown that the activation of ERK1/2 resulting in Elk-1 phosphorylation in striatal neurons supporting the hypothesis that prolonged exposure to substance abuse causes a dysregulation of MAPK pathway.

The self-reported impact of legal and non-legal sanctions on a group of recidivist drink drivers

Concern remains regarding the efficacy of legal sanctions to reduce drink driving behaviours among repeat offenders. The present study examined the impact of traditional legal sanctions (e.g., fines and licence disqualification periods), nonlegal sanctions, alcohol consumption and the frequency of recent offending behaviour(s) on intentions to re-offend for a group of recidivist drink drivers (N=166). The analysis indicated that participants perceived legal sanctions to be severe, but not entirely certain nor swift. In addition, self-reported recent drink driving behaviours and alcohol consumption levels were identified as predictors of future intentions to drink and drive. The findings of the study confirm the popular assumption that some repeat offenders are impervious to the threat and application of legal sanctions and suggests that additional interventions such as alcohol treatment programs are required if the drinking and driving sequence is to be broken for this population. (c) 2005 Elsevier Ltd. All rights reserved.

A comprehensive assessment of self -report experiences of adoptive parents of special needs children in Florida

Adoption of special needs children is now seen as a life long event whereby the adoptive child and family have unique needs. The need for postplacement resources throughout the life cycle of the adoption process is evident. This exploratory-descriptive research employed a random stratified cross-sectional design. The purpose of the study was to describe, identify, examine, and assess the relative influence of identified empirically and conceptually relevant variables of self-report experiences of adoptive parents of special needs children. Primary areas of exploration included: (1) adoptive children and families' characteristics, (2) postplacement service needs, utilization and satisfaction, and (3) adoptive parents' perceptions of their adoption experiences. A proportionate stratified random mail survey was used to obtain 474 families who had adopted special needs children from the 15 geographic districts which make up the state adoption social service agency in Florida. A 144-item survey questionnaire was used to collect basic information on demographic data, service provision, and adoption experiences. Four research questions were analyzed to test the effect the predictor variables had on willingness to adopt another special needs child, successful adoption, satisfying experience, and realism about problems. All four research questions revealed that the full model and the child's antecedent and the adoptive parents' intervening variable blocks were significant in explaining the variance in the dependent variables. The child's intervening variables alone were only significant in explaining the variance for one of the dependent variables. The results of the statistical analysis on the fifth research question and the three hypotheses determined that (1) only one postplacement service, crisis intervention, had a statistically significant impact on the adoptive parents' perceived level of satisfaction with the adoption experience; (2) adoptive parents who rate their adoption as successful are more likely to express a desire to adopt another special needs child; (3) the more adequate information on the child the adoptive parents perceived that they had prior to placement, the more they perceived they were realistic about the problems they would encounter; and (4) six specific postplacement services were found to be significant in predicting successful adoptions--crisis intervention, outpatient drug/alcohol treatment, maintenance subsidy, physical therapy, special medical equipment, and family counseling. Implications for the social work field and future research are discussed. ^

The families and friends of heavy drinkers: Caught in the cross-fire of policy change?

INTRODUCTION AND AIMS: Research highlights the need to better understand the impact of alcohol-related harm on families and communities. Scottish policy initiatives to reduce alcohol consumption and alcohol-related harm include the planned introduction of a minimum unit price for alcohol. We aimed to explore existing and proposed changes in alcohol policy, from the standpoint of heavy drinkers, through accounts of their involvement and repercussions for family and friends. DESIGN AND METHODS: Interviews were conducted with 20 heavy drinkers, recruited from hospital alcohol treatment centres in Scotland's two largest cities. Participants were part of a larger longitudinal mixed methods study. Interviews explored experiences of alcohol-related harm and the impact, or potential impact, of alcohol policy changes on drinking patterns, risk-taking, consumption and wellbeing. Data coded for 'family and friends' were thematically analysed using a constant comparison method. RESULTS: Family and friends were portrayed as important for aiding moderation and abstinence, but more often for sustaining continued heavy drinking. Heavy drinkers with complex needs and those living in deprived communities suggested that increased alcohol prices could exacerbate the detrimental effect on their health and social circumstances, and that of their family, should their consumption remain excessive. DISCUSSION AND CONCLUSIONS: Population level policy initiatives to reduce alcohol consumption, such as minimum unit pricing, will impact on the families and social networks of heavy drinkers in addition to the drinker. The most vulnerable may be affected disproportionately. Alcohol policy changes and evaluations need to consider consequences for drinkers, families and communities. [O'May F, Whittaker A, Black H, Gill J. The families and friends of heavy drinkers: Caught in the cross-fire of policy change?

Tests of the elaborated intrusion theory of craving and desire : features of alcohol craving during treatment for an alcohol disorder

Objectives. We tested predictions from the elaborated intrusion (EI) theory of desire, which distinguishes intrusive thoughts and elaborations, and emphasizes the importance of imagery. Secondarily, we undertook preliminary evaluations of the Alcohol Craving Experience (ACE) questionnaire, a new measure based on EI Theory. Methods. Participants (N ¼ 232) were in correspondence-based treatment trials for alcohol abuse or dependence. The study used retrospective reports obtained early in treatment using the ACE, and daily self-monitoring of urges, craving, mood and alcohol consumption. Results. The ACE displayed high internal consistency and test – retest reliability and sound relationships with self-monitored craving, and was related to Baseline alcohol dependence, but not to consumption. Imagery during craving was experienced by 81%,with 2.3 senses involved on average. More frequent imagery was associated with longer episode durations and stronger craving. Transient intrusive thoughts were reported by 87% of respondents, and were more common if they frequently attempted to stop alcohol cognitions. Associations between average daily craving and weekly consumption were seen. Depression and negative mood were associated with more frequent, stronger and longer lasting desires for alcohol. Conclusions. Results supported the distinction of automatic and controlled processes in craving, together with the importance of craving imagery. They were also consistent with prediction of consumption from cross-situational averages of craving, and with positive associations between craving and negative mood. However, this study’s retrospective reporting and correlational design require that its results be interpreted cautiously. Research using ecological momentary measures and laboratory manipulations is needed before confident inferences about causality can be made.