Binding sites for substance P(1-7), SP(1-7) have been identified and characterized for the first time in crude membrane fraction from rat CNS using tritiated ([3H]) SP(1-7) as tracer. These putative receptors were investigated in relation to their affinity for tachykinins, opioid peptides and sigma receptor ligands. [3H]-SP(1-7) specifically binds to high affinity binding sites identified as receptor targets for the heptapeptide SP (1-7). Two distinct binding sites were observed in the spinal cord. One site is recognized by high affinity for SP(1-7) with a Kd of 0.5 nM, whereas the other site showed low affinity for the heptapeptide (Kd=12 nM). In the brain, the binding of SP(1-7) fitted a single site binding model with a Kd of 4.4 nM and a Ki of 4.2 nM. Further, using the spinal cord membranes the binding of [3H]-SP (1-7) was weakly displaced by SP and other N-terminal fragments thereof and no or negligible affinity was observed for ligands of the NK-1, NK-2 and NK-3 tachykinin receptors, C-terminal SP(5-11), Tyr-w-MIF-1 or the mu-opioid receptor antagonists naloxone and naloxonazine. On the other hand it was significantly displaced by endomorphin-2, DAMGO, and Try-MIF-1 and exhibit some affinity for MIF-1, ß-casomorphin and endomorphin-1. However, only endomorphin-2, DAMGO and Tyr-MIF-1 showed affinity in the close range of the native peptide SP(1-7). The affinity of endomorphin-2 for the spinal cord site was 10 times lower than that of SP(1-7) but more than 100 times higher than the affinity recorded for endomorphin-1. Tyr-MIF-1 but not Tyr-w-MIF-1 showed similar affinity as endomorphin-2 for SP(1-7) site. All peptides exhibiting high affinity at the SP(1-7) site, have a phenylalanine or a leucine residue in their C-terminal structure. Further, synthetic analogues of SP(1-7) were tested for their affinity for the SP(1-7) receptor in the rat spinal cord. An important finding here was that the receptor-ligand-interaction was favoured by the C-terminal region of SP(1-7). Residues at positions 5-7 appeared crucial for binding to the specific SP(1-7) site. The presence of the amidated Phe7 residue was extremely critical for binding to the SP(1-7) site.The analogue Gln5-Gln6-Phe7-NH2 was almost equipotent with the parent peptide in the SP (1-7) receptor binding assay. Furthermore, the SP(1-7)-amide potently and dose dependently reduced several signs of the reaction to morphine withdrawal and was significantly attenuated by the addition of the sigma agonist SK-10047. In conclusion, the work presented in this thesis has contributed the characterization of the properties of highly selective binding sites for SP(1-7) in the rat spinal cord and VTA. These sites appear to be distinct from the µ-opioid receptor or any of the known neurokinin receptors. The study further indicates that the SP(1-7)-amide mimics the effect of the nativ heptapeptide and that the mechanisms for its action involve a sigma receptor site.

<p>Syftet med studien är att belysa hur barn i åldrarna tre till fem år tänker kring genus. Barnen fick lyssna på sagan ”Prinsessan Papperspåse” (Robert N. Munsch, 1980) och intervjuades sedan med utgångspunkt från sagan. Resultatet visar att barnen tänker relativt lika kring genus oberoende av kön och ålder. Både flickorna och pojkarna hade tydliga föreställningar om vad som är ett acceptabelt uppträdande av det motsatta könet. Framför allt hade de klara tankar om hur en flicka ska se ut om hon ska gifta sig. Att vara smutsig är för barnen inte acceptabelt, vare sig man är flicka eller pojke. Utan undantagsvis lade flickorna fokus på relationen mellan prinsessan och prinsen medan pojkarna lade fokus mer på draken och prinsen.</p>

<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.

<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>

<p>Anabolic-androgenic steroids (AAS) have been used in clinics for decades. The misuse of AAS has previously been attributed merely to sport athletes, taking AAS with intentions to increase muscle mass, enhance physical performance and to improve results in competitions. Today, the misuse of AAS has spread to adolescents and young adults not connected to sports. Alarmingly, many reports are pointing at severe psychiatric adverse effects among AAS abusers, which include mood swings, mania, anxiety, depression and aggression. Numerous examples of severe and often unprovoked violence and brutal crimes have been connected to AAS abuse and there is a strong need for a better understanding of the underlying biochemical events that might account for the adverse behaviors induced by AAS. The general aim of this thesis was to study the effect of chronic AAS administration on neuropeptide circuits in the rat brain associated with the regulation of rewarding effects, memory, anxiety, depression and aggression, using nandrolone decanoate as a prototype AAS.</p><p>Results demonstrated that daily administration of AAS to rats in doses comparable to those taken by AAS abusers, in certain brain structures significantly affected, <i>a</i>) the levels of the opioid peptides dynorphin B and Met-enkephalin-Arg⁶Phe⁷, <i>b</i>) the levels of the tachykinin substance P (SP), <i>c</i>) the density of the SP neurokinin 1 (NK1) receptor, <i>d</i>) the level of the SP metabolite SP_1-7that frequently exerts opposite effects to SP, <i>e</i>) the SP_1-7generating enzyme substance P endopeptidase (SPE) and finally, <i>f</i>) the levels of the neuropeptide calcitonin gene-related peptide (CGRP) often co-localized with SP. The alterations seen in the levels and activities of these neurochemical components are in many aspects compatible with behaviors typified among AAS abusers.</p>

Anabolic-androgenic steroids (AAS) have been used in clinics for decades. The misuse of AAS has previously been attributed merely to sport athletes, taking AAS with intentions to increase muscle mass, enhance physical performance and to improve results in competitions. Today, the misuse of AAS has spread to adolescents and young adults not connected to sports. Alarmingly, many reports are pointing at severe psychiatric adverse effects among AAS abusers, which include mood swings, mania, anxiety, depression and aggression. Numerous examples of severe and often unprovoked violence and brutal crimes have been connected to AAS abuse and there is a strong need for a better understanding of the underlying biochemical events that might account for the adverse behaviors induced by AAS. The general aim of this thesis was to study the effect of chronic AAS administration on neuropeptide circuits in the rat brain associated with the regulation of rewarding effects, memory, anxiety, depression and aggression, using nandrolone decanoate as a prototype AAS. Results demonstrated that daily administration of AAS to rats in doses comparable to those taken by AAS abusers, in certain brain structures significantly affected, a) the levels of the opioid peptides dynorphin B and Met-enkephalin-Arg6Phe7, b) the levels of the tachykinin substance P (SP), c) the density of the SP neurokinin 1 (NK1) receptor, d) the level of the SP metabolite SP1-7 that frequently exerts opposite effects to SP, e) the SP1-7 generating enzyme substance P endopeptidase (SPE) and finally, f) the levels of the neuropeptide calcitonin gene-related peptide (CGRP) often co-localized with SP. The alterations seen in the levels and activities of these neurochemical components are in many aspects compatible with behaviors typified among AAS abusers.