A contemporary history of ibogaine in the United States and Europe.
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Europe↗
Biomedical subjects
C D Kaplan
Publications and source records attributed to C D Kaplan.
Spt5 and spt6 are associated with active transcription and have characteristics of general elongation factors in D. melanogaster.
The Spt4, Spt5, and Spt6 proteins are conserved throughout eukaryotes and are believed to play critical and related roles in transcription. They have a positive role in transcription elongation in Saccharomyces cerevisiae and in the activation of transcription by the HIV Tat protein in human cells. In contrast, a complex of Spt4 and Spt5 is required in vitro for the inhibition of RNA polymerase II (Pol II) elongation by the drug DRB, suggesting also a negative role in vivo. To learn more about the function of the Spt4/Spt5 complex and Spt6 in vivo, we have identified Drosophila homologs of Spt5 and Spt6 and characterized their localization on Drosophila polytene chromosomes. We find that Spt5 and Spt6 localize extensively with the phosphorylated, actively elongating form of Pol II, to transcriptionally active sites during salivary gland development and upon heat shock. Furthermore, Spt5 and Spt6 do not colocalize widely with the unphosphorylated, nonelongating form of Pol II. These results strongly suggest that Spt5 and Spt6 play closely related roles associated with active transcription in vivo.
Animals↗
Post-transcriptional control of cyclooxygenase-2 gene expression. The role of the 3'-untranslated region.
The cyclooxygenase (COX)-2 enzyme is responsible for increased prostaglandin formation in inflammatory states and is the major target of nonsteroidal anti-inflammatory drugs. Normally COX-2 expression is tightly regulated, however, constitutive overexpression plays a key role in colon carcinogenesis. To understand the mechanisms controlling COX-2 expression, we examined the ability of the 3'-untranslated region of the COX-2 mRNA to regulate post-transcriptional events. When fused to a reporter gene, the 3'-untranslated region mediated rapid mRNA decay (t(1/2) = 30 min), which was comparable to endogenous COX-2 mRNA turnover in serum-induced fibroblasts treated with actinomycin D or dexamethasone. Deletion analysis demonstrated that a conserved 116-nucleotide AU-rich sequence element (ARE) mediated mRNA degradation. In transiently transfected cells, this region inhibited protein synthesis approximately 3-fold. However, this inhibition did not occur through changes in mRNA stability since mRNA half-life and steady-state mRNA levels were unchanged. RNA mobility shift assays demonstrated a complex of cytoplasmic proteins that bound specifically to the ARE, and UV cross-linking studies identified proteins ranging from 90 to 35 kDa. Fractionation of the cytosol showed differential association of ARE-binding proteins to polysomes and S130 fractions. We propose that these factors influence expression at a post-transcriptional step and, if dysregulated, may increase COX-2 protein as detected in colon cancer.
3T3 Cells↗
How ageing and social factors affect memory.
OBJECTIVES: To explore the relationships between lifestyle and memory, and determine whether social factors influence memory. METHODS: the relationship between memory and lifestyle was examined in 497 adults aged 25-80 years, using the Mectamemory in Adulthood questionnaire. We asked about sports activity and perceived activity, participation in voluntary organizations and social contacts. RESULTS: Activity and frequent contact with friends and family were related to higher memory capacity scores. Those with higher capacity scores were also younger, had better health and a stronger internal locus of control. In contrast, people with higher anxiety scores had more symptoms and less education, and were more externally oriented. CONCLUSIONS: people who consider themselves socially and physically active also consider their memory capacity to be good and are less anxious about their memory than less socially and physically active people. Perceived memory change appears to be predominantly influenced by ageing, whereas memory capacity and memory anxiety are more influenced by social factors.
Adult↗
The design and effectiveness of therapeutic community research in Europe: an overview.
An overview of the state of the art of research on the treatment services of the therapeutic community for drug addicts in Europe is presented. This research tradition has largely been fragmented and local in its implementation. There has been a scientific gap concerning evaluation research and the treatment services offered by the therapeutic community. The American research antecedents to the European tradition are reviewed. The essential European groups, research designs and results are presented for each country with something greater than an ad hoc study experience. The strengths and weaknesses of the research designs, results and organizations are critically assessed. Recommendations for future research are presented and referenced to specific recommendations for therapeutic community research coming out of an American National Institute on Drug Abuse Technical Review. Among the conclusions of the overview is the need for more qualitative phenomenological research to complement the existing quantitative approach.
Community Mental Health Services↗
L-Methadone and D,L-methadone in methadone maintenance treatment: a comparison of therapeutic effectiveness and plasma concentrations.
The clinical effectiveness of l-methadone maintenance treatment (LMMT) carried out using d,l-methadone or l-methadone have been compared with ambulatory heroin-dependent subjects. A total of 40 heroin-dependent subjects, previously maintained on l-methadone in Frankfurt am Main, were divided into two groups under randomised double-blind conditions and received either an equivalent dose of l-methadone as d,l-methadone or remained on the previous l-methadone treatment. Requests for a change in the dose of d,l-methadone and l-methadone were recorded, urine samples for determination of illicit drug use were collected and the individual level of opiate craving was determined over a 22-day observation period. There was no significant difference between the two groups in the number requests for a dose change (dose increase <10%). However, there was a significant increase in heroin use in the group which continued to receive l-methadone. Although there was less variability in opiate craving in the group receiving d,l-methadone, the mean intensity of opiate craving did not differ between the two groups. The mean l-methadone dose:l-methadone plasma concentration ratio, an index of the bioavailability of l-methadone in individual subjects, showed no significant change when the treatment was changed to d,l-methadone. The mean d-methadone:l-methadone plasma concentration ratio was 1.17. There was no significant difference between these ratios for day 15 and day 22. The mean l-methadone:EDDP plasma concentration ratio in the l-methadone group was 22.2 and the d,l-methadone:EDDP plasma concentration ratio was 18.4 . The plasma EDDP concentration in the d,l-methadone group increased 3-fold after starting treatment with d, l-methadone. These findings suggest that d,l-methadone can be used in methadone maintenance treatment of heroin-dependent subjects but that further studies are required to evaluate pharmacokinetic interactions between methadone enantiomers.
Adult↗
The legal importation of prescription drugs into the United States from Mexico: a study of Customs declaration forms.
The nature and magnitude of the problem of the diversion of prescription drugs from legal to illegal markets have been identified as a high priority by the federal government. This study was based on a random sample (2,005) of declaration forms of persons declaring Mexican prescription drugs at the US Customs office in Laredo, Texas. Of the 75 different types of drugs, the most frequently declared drugs were Valium (71%), Rohypnol (46%), and Tafil (25%), drugs highly associated with nonmedicinal use among United States teenagers and young adults. These data reinforce a documented need for more transnational cooperative efforts between the United States and Mexico.
Adult↗
Psychiatric diagnosis in addiction treatment experiments.
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Humans↗
A comparison of alcohol, drugs, and aggressive crime among Mexican-American, black, and white male arrestees in Texas.
Few comparative studies exist examining the relationship between substance abuse and aggressive behavior under different social conditions. We studied the relationship between aggressive crime and substance abuse among Mexican-American, black and white male arrestees in Dallas, Houston, and San Antonio, Texas using existing 1992 Drug Use Forecasting (DUF) data. The aim of the analysis was to predict the outcome of aggressive crime from drug and alcohol-related and ethnic group variables within the total male sample (n = 2,364). Results indicated that ethnicity was significantly related to aggressive crime. Mexican-American arrestees were more likely to be arrested for aggressive crimes than either blacks or whites. Drug and alcohol use effects were found across all ethnic groups. In general, the subgroup which drank frequently and tested positive for drug use was less likely to be charged with aggressive crimes than the other subgroups. The psychopharmacological influence of alcohol as a disinhibitor and drugs as a inhibitor provides one explantation of the results. Specific ethnic subcultural and ecological influences also affect the outcome. Our study strongly indicates the heterogeneous character of the drug using population in relation to aggression. The variability between subculturally defined subgroups requires detained ethnographic field studies in the future to describe the contexts of substance use and aggressive behavior.
Black or African American↗
Risk contexts and risk behaviors in the Euregion Maas-Rhein: the Boule de Neige intervention for AIDS prevention among drug users.
Using targeted sampling, self-reported data of 1,767 drug users in the Euregion Maas-Rhein were collected over 3 years. Forty-two percent of the injection drug users shared syringes with sexual partners and 47.8% with friends. Eighty-one percent of the total sample had sexual contact in the last 6 months, half of whom with one person and half with two or more. Significant predictors of high-risk drug use were injecting in the presence of others, injection onset before the age of 20, female gender, and not living in The Netherlands. Participation in needle exchange or methadone programs and sufficient knowledge of risk factors was not significantly related to a reduction of high-risk drug use behavior. High-risk sexual behavior was found to be related to male gender, under the age of 30 and to multiple sexual partners. We conclude that in a social context where needle exchange, methadone programs, and sufficient knowledge of risk factors among the drug user population exist, AIDS prevention can be improved through behavioral skills training and developing specific interventions that target the peer group environments, rituals, partner relationships, and lifestyles of drug users.
Acquired Immunodeficiency Syndrome↗
The social network characteristics of fibromyalgia patients compared with healthy controls.
OBJECTIVE: To assess structural social network characteristics and perceived loneliness in fibromyalgia syndrome (FMS) patients and healthy controls. METHODS: A cross-sectional, retrospective, case-control design was employed using a structured interview and a self-report questionnaire. We studied 25 female FMS patients and 25 matched healthy female controls. RESULTS: FMS patients had statistically significantly (P < 0.05) more intimate friends (mean 4.5) and more health care providers (mean 1.5) than did controls (2.3 and 0.0, respectively). The FMS patients more often initiated the contact with family members (mean 2.1) than did controls (mean 0.8). FMS patients did not perceive themselves as lonelier than controls perceived themselves. While there was a significant negative correlation between loneliness and social network variables among the controls, this relationship was not significant among the FMS patients. Among the patients, there was a strong correlation between the total social network size and the number of intimate friends, whereas in controls, the mean number of acquaintances was strongly correlated with the total network size. CONCLUSION: Compared to healthy controls, the social networks of FMS patients presented more linkages with intimate friends, family members, and health care providers. The lack of correlation between loneliness and social network variables for FMS patients is not what might be expected from social support theory. The assessment of structural social network characteristics along with social support variables may add to our understanding of the social functioning of FMS patients.
Adult↗
Retinal degeneration characterizes a spinocerebellar ataxia mapping to chromosome 3p.
A heterogeneous group of neurological disorders known as the spinocerebellar ataxias (SCA) are characterized by degeneration of the cerebellum, spinal cord and brainstem. We describe linkage analysis in four unusual SCA families revealing a distinct disease locus on chromosome 3p14-21.1. The disease in these families is distinguished from other forms of SCA by concomitant retinal degeneration. Initial visual problems leading to blindness, disabling ataxia and anticipation are seen in all kindreds. The anticipation in these families suggests a dynamic mutation at this locus. Eventual molecular characterization of this disease may provide valuable insights into the processes of both neural and retinal degeneration.
Adolescent↗
The daily life of heroin-addicted persons: the biography of specific methodology.
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Culture↗
The prevention of stimulant misuse.
The term 'stimulant' refers to a class of drugs that increase psychophysiological arousal. From the viewpoint of prevention, it is more useful to look primarily at the social consequences and functions of stimulants. Every society has a documented use of stimulants. When planning interventions the dynamics of use must be placed in the foreground. Stimulant epidemics, like problematic stimulant users, have a natural tendency to burn themselves out. Different types of stimulants may differ in their origins, but their epidemiological consequences and use functions tend to be similar. Implications for prevention can be drawn from the characteristics of stimulant use epidemics. Users at risk for socially unacceptable patterns should be targeted for prevention efforts. Mass media campaigns that single out stimulants should be avoided. Much of the harm associated with stimulants is a consequence of life-styles characterized by polydrug use and unhealthy practices. Prevention should be timed to the appropriate period of the epidemic. Interventions useful at period 1 will not work at period 2. The recommendations of the WHO Advisory Group on the Adverse Effects of Cocaine and Coca provide a good model for primary, secondary and tertiary prevention for all forms of stimulant misuse. Stimulant prevention must be creative in finding ways of encouraging the movements of the drug to the periphery of users' lives.
Amphetamines↗
Are there 'casual users' of cocaine?
Medical and public opinion about cocaine use have shifted dramatically over the past decade. New research methodologies and definitions to evaluate the impact of cocaine are needed. This paper presents a theoretical definition and empirical analysis of the 'casual user' of cocaine. Data have been drawn from a subsample of 58 cocaine users and their cocaine-using contacts in Rotterdam. The methodology of the study presents a novel approach to patterns of cocaine use involving the integration of social network variables with 'snowball' sampling data collection techniques. The theoretical definition is systematically related to two social context variables: (1) the scope of settings where contacts use cocaine; (2) the degree of involvement in social network relations of actual cocaine use. Scope of settings has been defined in terms of the number of cocaine-using social circuits contacts are drawn from: i.e. 'narrow' setting where all contacts originate from one circuit while a 'wide' setting indicates contacts come from two or more circuits. Involvement has been defined in terms of the percentage of contacts where the relation with study participants is characterized by cocaine use most or all of the time. Additional social network variables measuring the mean duration (in years) of contacts' cocaine use and the use of cocaine with contacts in the last six months are subsequently related to the scope and involvement variables. The implications of the analysis for a new cross-classification of cocaine use patterns are discussed with special reference to public health policy issues.
Analysis of Variance↗
Prevalence of psychopathology in drug-addicted Dutch.
In Dutch samples of treated heroin addicts, high prevalences of a heterogeneous psychiatric co-morbidity can be found with regard to Diagnostic and Statistical Manual (third edition) (DSM-III) classifications, Zung Depression Inventory, and sum scores of a 90-item Symptom Checklist (SCL-90). A high-threshold (N = 87) and a low-threshold (N = 116) program are compared with regard to psychopathology and severity of psychopathology. A consecutive admissions design was used. More than 50% of the respondents suffered from a lifetime DSM-III Axis I disorder (70% with antisocial personality disorder included), and 40% were still suffering from one of the disorders in the year preceding the interview. Schizophrenia was diagnosed five times as much as in normal population samples (5%). The most frequently diagnosed disorders were recurrent major depression, phobic disorders, alcohol abuse and dependence, dysthymic disorder, and antisocial personality disorder. The prevalences of DSM-III disorders, the total number of symptoms, and the score on the Zung Depression Inventory and 90-item Symptom Checklist were all significantly higher in treatment-seeking drug addicts entering the high-threshold program. Within each program, three clinically meaningful subgroups can be distinguished: one group with DSM-III Axis I lifetime or current psychopathology and/or antisocial personality disorder, one with antisocial personality disorder only, and one with neither DSM-III psychopathology nor antisocial personality disorder. Possibly, self-selection results in patients with more serious conditions entering more treatment-oriented facilities. Odds ratios show that schizophrenia and mood disorders and especially associated on a lifetime and current basis.
Adult↗
The effects of orally active enkephalinase inhibitors on morphine withdrawal syndrome.
Considerable evidence has accumulated to suggest that intracerebroventricular administration of enkephalinase inhibitors, which do not penetrate the blood-brain barrier, significantly attenuates opioid withdrawal syndrome. Therefore, the aim of this study was to examine the effect of intraperitoneal (i.p.) administration of orally active enkephalinase inhibitors, acetorphan (2.5-20 mg kg-1) and SCH 34826 (15-120 mg kg-1). These drugs significantly decreased the severity of the naloxone precipitated withdrawal syndrome in morphine dependent rats and mice. It therefore appears that these orally active enkephalinase inhibitors are promising tools in studying modulation of opioid dependence phenomena.
Administration, Oral↗
Drug use contexts and HIV-consequences: the effect of drug policy on patterns of everyday drug use in Rotterdam and the Bronx.
Epidemiological data on HIV seroprevalence has been essential in assessing the (future) extent of the AIDS epidemic. By coupling these data with quantifiable variables related to injection drug use (frequency of injecting, number of needle sharing partners) specific 'risk behaviors' could be determined, accounting for the rapid spread of the virus in the injecting drug user (IDU) population. Yet, such data give little information on the social mechanisms and setting generating such risk behaviors. In order to understand the transmission of HIV among the IDU population one needs to study the micro settings and social context of drug use. This paper describes and explores certain patterns of drug use, sharing, and natural support systems found amongst IDUs in two very different cities, Rotterdam (The Netherlands) and the Bronx, New York City (USA). By specifying details of the micro-settings of everyday drug use in both locales, it is possible to identify certain common elements and consequences of personal and social behavior driven by drug use per se (e.g. drug preference), and to differentiate these from behaviors and consequences determined by drug policy and the social context in which drug use actually occurs. These policies and the social context they create can in turn be shown to relate to risks for HIV transmission, e.g. the increased likelihood of sharing injection equipment. A more careful ethnographic approach, taking advantage of natural experimental opportunities, comparisons and controls, may be utilized to examine drug-related behaviors in their social context and to better assess their relevance to public health--especially to AIDS.
Cross-Cultural Comparison↗