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<p>Dyskinesias or abnormal involuntary movements are a debilitating complication of long-term levodopa treatment of Parkinson’s disease (PD) that is widely experienced and may compromise the efficacy of the drug therapy. Tardive dyskinesia is another important adverse effect seen with antipsychotic drug treatment. The neural mechanisms underlying levodopa- and neuroleptic-induced dyskinesia are not clear and involvement of the endogenous opioid neuropeptide system has been implicated. In this thesis, the role of the opioid system is investigated in models of dyskinesia and PD using behavioral, neurochemical and advanced analytical chemistry techniques. In addition, the motor effects of a new partial dopamine agonist with normalizing properties on both reduced and elevated dopamine transmission are studied and a new model for tardive dyskinesia is presented.</p><p>Using microdialysis in combination with micro-electrospray mass spectrometry, the <i>in vivo</i> processing of the opioid neuropeptide dynorphin A(1-17) was studied and 32 metabolites were detected in the striatum. Altered <i>in vivo</i> metabolism of the peptide was found in a model of PD with more metabolites formed in the dopamine-depleted striatum. Moreover, dynorphin A(1-17) was differently processed in levodopa-, bromocriptine and saline-treated animals. </p><p>Levodopa treatment caused an increase in the mRNA expression of the precursor of dynorphin, preproenkephalin-B as well as the precursor of enkephalin, preproenkephalin-A, in all sub-regions of the dopamine-depleted striatum. A non-selective opioid receptor antagonist, naloxone, was found to reduce levodopa-induced dyskinesia with maintained antiparkinsonian response and a normalization of hyperkinesia. Moreover, the new drug GMC1111 showed dopamine stabilizing properties in models of levodopa-induced dyskinesia and PD. This might prove useful in the treatment of PD.</p><p>Altogether, these results suggest that the endogenous opioid system is involved in the pathophysiology of levodopa-induced dyskinesia.</p>

Dyskinesias or abnormal involuntary movements are a debilitating complication of long-term levodopa treatment of Parkinson’s disease (PD) that is widely experienced and may compromise the efficacy of the drug therapy. Tardive dyskinesia is another important adverse effect seen with antipsychotic drug treatment. The neural mechanisms underlying levodopa- and neuroleptic-induced dyskinesia are not clear and involvement of the endogenous opioid neuropeptide system has been implicated. In this thesis, the role of the opioid system is investigated in models of dyskinesia and PD using behavioral, neurochemical and advanced analytical chemistry techniques. In addition, the motor effects of a new partial dopamine agonist with normalizing properties on both reduced and elevated dopamine transmission are studied and a new model for tardive dyskinesia is presented. Using microdialysis in combination with micro-electrospray mass spectrometry, the in vivo processing of the opioid neuropeptide dynorphin A(1-17) was studied and 32 metabolites were detected in the striatum. Altered in vivo metabolism of the peptide was found in a model of PD with more metabolites formed in the dopamine-depleted striatum. Moreover, dynorphin A(1-17) was differently processed in levodopa-, bromocriptine and saline-treated animals. Levodopa treatment caused an increase in the mRNA expression of the precursor of dynorphin, preproenkephalin-B as well as the precursor of enkephalin, preproenkephalin-A, in all sub-regions of the dopamine-depleted striatum. A non-selective opioid receptor antagonist, naloxone, was found to reduce levodopa-induced dyskinesia with maintained antiparkinsonian response and a normalization of hyperkinesia. Moreover, the new drug GMC1111 showed dopamine stabilizing properties in models of levodopa-induced dyskinesia and PD. This might prove useful in the treatment of PD. Altogether, these results suggest that the endogenous opioid system is involved in the pathophysiology of levodopa-induced dyskinesia.

<p>The endogenous opioid enkephalin neuropeptides are mediators of pain perception and have been implicated in human addictions. The preproenkephalin gene and its mRNA have also provided many examples of tissue- and species-specific variations in mRNA structure produced through a variety of transcriptional and post-transcriptional mechanisms. Resultant differences in mRNA structure, in several cases, have impact on translation of enkephalin prepropeptide. The reports and discussion presented herein describe studies of the preproenkephalin gene and mRNA structure in the guinea pig, an animal that may have specific advantages for modeling the human endogenous opioid system. A guinea pig brain cDNA library was constructed and screened for clones of preproenkephalin and preprodynorphin, which were then sequenced. These studies confirmed the predicted mRNA structure that had been previously proposed based on homology with gene sequences and other methods. Multiple transcription initiation sites for each of these prepropeptide genes were also identified. Studies were conducted in the guinea pig to evaluate the effects of the administration of cocaine in a “binge” paradigm for two and seven days on preproenkephalin mRNA levels in several brain regions. “Binge” cocaine administration for seven (but not two) days resulted in differential changes in mRNA levels in different brain regions. Decreases were observed in the nucleus accumbens and hypothalamus, and increases in the frontal cortex, amygdala and hippocampus. These findings differ from those of previous rodent studies and suggest that this species may provide a useful alternative model for the study of the effects of cocaine on preproenkephalin gene expression in the human brain. Human genetic studies were also conducted in opioid-dependent (formerly heroin-addicted) and control subjects to test the hypothesis that the preproenkephalin gene is associated with heroin addiction. In two separate studies, we obtained evidence that this gene may be associated with the development of human heroin addiction.</p>

The endogenous opioid enkephalin neuropeptides are mediators of pain perception and have been implicated in human addictions. The preproenkephalin gene and its mRNA have also provided many examples of tissue- and species-specific variations in mRNA structure produced through a variety of transcriptional and post-transcriptional mechanisms. Resultant differences in mRNA structure, in several cases, have impact on translation of enkephalin prepropeptide. The reports and discussion presented herein describe studies of the preproenkephalin gene and mRNA structure in the guinea pig, an animal that may have specific advantages for modeling the human endogenous opioid system. A guinea pig brain cDNA library was constructed and screened for clones of preproenkephalin and preprodynorphin, which were then sequenced. These studies confirmed the predicted mRNA structure that had been previously proposed based on homology with gene sequences and other methods. Multiple transcription initiation sites for each of these prepropeptide genes were also identified. Studies were conducted in the guinea pig to evaluate the effects of the administration of cocaine in a “binge” paradigm for two and seven days on preproenkephalin mRNA levels in several brain regions. “Binge” cocaine administration for seven (but not two) days resulted in differential changes in mRNA levels in different brain regions. Decreases were observed in the nucleus accumbens and hypothalamus, and increases in the frontal cortex, amygdala and hippocampus. These findings differ from those of previous rodent studies and suggest that this species may provide a useful alternative model for the study of the effects of cocaine on preproenkephalin gene expression in the human brain. Human genetic studies were also conducted in opioid-dependent (formerly heroin-addicted) and control subjects to test the hypothesis that the preproenkephalin gene is associated with heroin addiction. In two separate studies, we obtained evidence that this gene may be associated with the development of human heroin addiction.

Introduction 1. The drug, an addictive substance, drug addiction and certain further relevant terms 2. Overview of the classification, evolution, characterization and effects of particular illegal drugs 3. Drug scene in the Czech Republic in and the drug phenomenon in the European context 4. Drug-related crime in the light of the offender 5. The legal regulation related to substance abuse 6. Prevention and the drug policy in the Czech Republic Conclusion Abbreviation list Used literature list Appendix list Appendix Summary

<p>Nästan 15 000 långtidssjukskrivna personer utförsäkrades sista december 2009! Arbetslinjen -att ta till vara människors arbetsförmåga och allas bidrag till välfärden - har präglat reformerandetav den svenska socialförsäkringen. Metoden blev en övergång från sjukskrivning tillarbetssökande genom en ny arbetsmarknadspolitisk åtgärd; Arbetslivsintroduktion. Programmetstartade januari 2010 vid Arbetsförmedlingen.Syftet med denna studie var att undersöka sex deltagares upplevelser av programmet Arbetslivsintroduktion.Urvalet hämtades från den population som tidigare haft sjukpenningeller tillfällig sjukersättning och som utförsäkrats 31 december 2009 samt deltagit i Arbetslivsintroduktionen2 januari – 31 mars 2010 vid en lokal Arbetsförmedling. Urvalsmetodenvar 1) självselektion och 2) bekvämlighetsurval. Sex kvalitativa intervjuer genomfördes. Dessaanalyserades med en kvalitativ innehållsanalys.Resultatet gav två teman; Deltagaren upplevde Arbetslivsintroduktionen som 1) påtvingadförändring och/eller innehållande 2) underlättande faktorer. I diskussionen relaterades resultatettill aktuell forskning om långtidssjukskrivna respektive arbetsmarknadsåtgärder, till regeringensintentioner med Arbetslivsintroduktionen samt till teorin KASAM. Studien påvisadeatt upplevelsen av Arbetslivsintroduktionen påverkades av många faktorer samt att resultatetstvå teman kunde relateras till deltagarens känsla av sammanhang (KASAM).Studien gav implikationer om upplevda brister under Arbetslivsintroduktionen vad gällerdialogen mellan olika rehabiliteringsaktörer, i synnerhet mellan sjukvård och Arbetsförmedling,men lyfte också frågor om samarbetet mellan Arbetsförmedlingen och Försäkringskassan.</p><p>Nyckelord: Arbetsmarknadsåtgärd, KASAM, Långtidssjukskriven, Samverkan,Återgång till arbete.</p>

<p><strong>Bakgrund: </strong>I dagens vårdarbete är behandling av venösa bensår en vanlig omvårdnadsåtgärd. Smärta, immobilitet samt social isolering relaterat till venösa bensår, är några av de faktorer som påverkar patientens livskvalitet. <strong>Syfte: </strong>Syftet med litteraturstudien var att beskriva hur sjuksköterskan på bästa sätt kan främja läkningen av venösa bensår. <strong>Metod: </strong>Beskrivande litteraturstudie sammanställd utifrån 14 kvantitativa samt sju kvalitativa studier publicerade mellan åren 2001 till 2009. Databaserna Cinahl och PubMed användes i sökningen av vetenskapliga artiklar. Sökorden som användes var Leg Ulcer, Nursing, Activity, Pain, Venous leg ulcer, Treatment, Management, Exercise, Bandages samt Psychological. <strong>Resultat: </strong>De omvårdnadsåtgärder som visade sig ha stor betydelse för sårläkning var kompression/sårvård, fysisk aktivitet, psykologiskt stöd samt eftervård. Sjuksköterskans kunskap och förmåga att kunna se patienten som en helhet var av stor vikt för god omvårdnad och förbättrad sårläkning. <strong>Slutsats: S</strong>juksköterskor behöver förbättra sina kunskaper angående sårvårdsbehandling. Sjuksköterskan bör ha en holistisk syn på patienten.</p><p> </p>

Ergebnisse einer breit angelegten Repräsentativerhebung zur Substitutionstherapie in Deutschland an 2694 Patienten zeigen, dass trotz hoher und komplexer Ko- und Multimorbidität mit psychischen Erkrankungen nur selten Psychiater an der Therapie beteiligt sind. Nur 16% der Substitutionsärzte (n=223) sind Psychiater oder Psychotherapeuten und nur 21% der substituierten Drogenabhängigen werden von Psychiatern behandelt. Die meisten substituierenden Psychiater sind in Institutsambulanzen psychiatrischer Kliniken tätig (51,3%), kaum in eigener Praxis (7,2%). Der Großteil der Substitutionsversorgung wird von Allgemein- und Hausärzten geleistet. Die relative Abstinenz psychiatrischer Kollegen bei der Substitution drogenabhängiger Patienten wird kritisch diskutiert. / Results of a nationally representative study in 2,694 patients reveal that most physicians (n=223) involved in substitution treatment of opioid-dependent patients are general practitioners, while only 16% have a psychiatric/psychotherapeutic background and only 21% of the addictive patients are treated by psychiatrists. This contrasts with the remarkably complex pattern of co- and multimorbidity with other mental disorders in such patients. Most psychiatrists engaged in substitution treatment work in specialized outpatient wards (51.3%), and few were operative in their own or private practice (7.2%). Implications of these critical findings are discussed.

The phenomen of drug dependence is one of the most problematic questions at present time. Drugs become much greater threat for youth, however even for children.Young people should direct their attention instead of passing experience with a drug in another direction especially try hard their selves-realization. In this direction there is a family support already important from childhood, the primary prevention both in the family setting and even at school and media influence is important as well.The fight with a drug sometimes resembles the fight with an unconquerable enemy. It can seem that it is useless to make any effort to this fight but I think that indifferent approach to this question is not right. Even one positive finished struggle with danger called the drug has sense to take as an example and believe in happy ends of all drug dependent adults, youth and children. The substance of the solution of drug dependence,the whole conception of this dependence and finding of a suitable therapeutic approach is often a subject of confusing and antagonistic interpretations. The therapy of this dependence is a long-termed and complicated process. It requires the first-rate judgement of a problem, certain time, finding of a suitable therapeutic programme as well or a therapist and a suitable therapeutic direction. The treatment of drug dependence involves not only a separate psychotherapeutic part, however also pharmacotherapy, concultation with other participant people, subjects and substance of a suitable application of psychotherapeutic technique. In my work I aim at success of individual variations of psychotherapeutic approaches in therapy of drug dependence as a fundamental point of work with a client. I prefer the investigation of dependence therapy on non-alcoholic drugs. Another aim of my research is to evaluate satisfaction of the clients with services of the treatment facilities in which they are treated now but also evaluation of experience with a relevant previous therapy. I am interested in comparison of clients´ and therapists´opinions on the therapy of drug dependence and the effectiveness of performing therapies in a mental home against a therapeutic community.