Abstract Title: Anabolic Androgenic Steroids – An analysis of how AAS is portrayed in Swedish media. Author: Jens Sundén Tutor: Philip Lalander Keywords: AAS, Anabolic steroids, social problems, media, drug abuse, gender The purpose of this study was to investigate how Anabolic Androgenic Steroids (AAS) are portrayed and described in the media, how AAS is constructed as a social problem, and how society in a social context uses knowledge and power for disciplinary and educational means. The study is based on the perception of AAS as a constructed social problem and analyzes the discourses surrounding AAS depicted in three Swedish newspapers. The sample was prepared on the basis that it represents different aspects of daily Swedish press. The method used in the paper is a discourse analysis with social constructivism and gender as theoretical tools used to analyze the sample material. An important conclusion of the analysis is that the use of AAS is a socially constructed problem, which incorporates both a stereotyped, aggressive male individual who desires an ideal body, and the use of AAS defined as an illegitimate abuse by society. Another important aspect of the analysis is how gender roles are highlighted in the sample and how these from a gender perspective are used to perpetuate male superiority and female subordination in society.

This is a study about gym training young men (age 18-20) and their attitude against anabolic androgenic steroids, AAS. In our study we examine if the muscular ideal in our society have any effect on young men and the young men’s attitude against their body and their training. We want to find out what attitude gym training young men have against AAS, and also what has had the influence to this attitude.          The study contains six qualitative performed interviews with young men who are training at the gym, which are based on relevant information about their training habits, nutritional supplement, influence, the muscular ideal, the gym culture and medias effect on young men when it comes to body ideals.            The young men’s attitudes is connected and compared to prior research about gym-training young men and what affects them to have a certain attitude against AAS, body and training. In our study we also use a theory by Giddens about social interaction and the late modern society we live in.           The conclusions of the result and analysis is that young men who trains at the gym for the purpose of getting bigger and in relation to the training takes nutritional supplements, have a more liberal attitude against AAS compared to those young men who doesn’t. Media, friends, equals at the gym and the gym culture are all factors that affect young men in their positive attitude in opposition to AAS.

Denna kvalitativa studie handlar om några behandlares upplevelser och erfarenheter kring vilka personer som hamnar i missbruk av anabola androgena steroider(AAS). Den belyser även vilken behanding som finns för problematiken. För att erhålla empiri används semistrukturerade intervjuer på fyra personer som arbetar med behandling av AAS. Resultatet visar att man kan kategorisera AAS-användare i tre olika grupper. När klienter kommer till behandling är det viktigt att man ser till helhetsbilden och att man ser varje individ för sig. Metoder som finns är terapi för det sjuka kroppsidealet, hjälp med träningsmissbruket, läkemedelsassisterad behandling samt annan psykosocial terapi. En intressant slutsats är att det finns hjälp att få vid AAS-missbruk, men tyvärr finns det inte resurser att hjälpa alla. Det finns fortfarande mycket kvar att lära inom ämnet och man behöver forska kring fler och bättre behandlingsmetoder som kan passa vid detta missbruk.

Neurotransmitters are widely distributed in the central nervous system of tilapia during development. In the present study, the effects of gonadal steroids, temperature, and neurotransmitters on the development of central neurotransmitter systems in tilapia, Oreochromis mossambicus, were investigated. Exogenous E2 before 10 days posthatching resulted in an inhibitory effect on the activity of central 5-HT system via decreasing TPH activity and increasing MAO activity, a decrease of the gene expression of brain aromatase and ERa, which is involved in the feminization. The masculinizing actions of 17a-methyltestosterone (MT) are most potent later at up to day 20 of age, and may depend on MT-induction of aromatase activity, aromatase mRNA gene expression and estrogen receptor-b mRNA gene expression. The development of central neurotransmitter systems is influenced by aquatic temperature during its respective restricted period. The influence of both lower and elevated temperatures on the neurotransmitter activity, either increasing or suppressing, is dependent on its developing stage. Neurotransmitters have an effect to influence the development of central neurotransmitter and this effect may mediated by the neural proliferation.

Recent changes in legislation and access to information, through sources such as the media, may have influenced peoples' expectations for information about their prescribed medication. As a result, health care professionals may perceive an increased pressure to provide information. A case study approach was employed to examine the sources and scope of information patients draw upon when they are prescribed oral steroids for asthma. The aim was to examine the extent to which patients can be said to exercise an `informed choice' when they take prescribed medication. The role and importance of GPs (general practitioners) in informing the choices patients make was also examined. Both qualitative and quantitative methods were employed. Interviews conducted with both patients and GPs indicated `gaps' in understanding. Although the GP was the preferred source of information, patients reported that the choices they made were based on information from a range of sources. General practitioners justified not providing information to patients so as to `protect' patients from knowledge of side effects. However, there was some awareness of the range of sources of information used by patients. A vignette technique was employed to further investigate GPs' recognition and understanding of the range of sources of information patients' use to inform the choices they make. Approximately half of the GPs who responded to the vignette recognised the influences presented. General practitioners who had been practising for a shorter period of time were significantly more likely to recognise these influences. The conclusions draw on the literature of the sociology of the professions. In spite of the way in which the Government has sought to encourage patients to act as consumers, the state has also continued to endorse GPs right to make decisions concerning the level of information to provide. If GPs do not believe it is in the interests of patients to be provided with information to make choices about their medications then the information available to patients may be limited. This will have an impact on the ease with which patients may make `medically' informed choices about their prescribed medication. Only when the communication between patients and GPs improves, will it be possible for a relationship to develop where patients may be assured of gaining information from their GP at the level they feel is appropriate to enable them to make informed choices about their medication.

Εστιάζοντας στα αποτελέσματα προσφάτων μελετών, οι οποίες είχαν ως θέμα τη διερεύνηση της σχέσης μεταξύ της χημικής δομής και της αντιλευχαιμικής δράσης, προκύπτει ότι το στεροειδικό τμήμα των ενώσεων που περιέχουν αλκυλιωτικούς παράγοντες, δεν αποτελεί μόνο τον βιολογικό φορέα των αλκυλιωτικών παραγόντων. Ο σχεδιασμός και η μελέτη παρόμοιων ενώσεων, οι οποίες έφεραν στη θέση 7 του στεροειδικού σκελετού μία αλλυλική κετόνη, παρουσίασαν μία σημαντικά αυξημένη αντιλευχαιμική δραστικότητα συγκριτικά με παράγωγα που περιείχαν στο μόριό τους έναν απλό στεροειδικό σκελετό. Προκειμένου να διερευνηθεί κατά πόσο η βελτίωση της αντιλευχαιμικής οφειλόταν στην εισαγωγή της 7-κετόνης ή του Δ5-7-κετο στεροειδικού συστήματος, αναγάγαμε το διπλό δεσμό στη θέση 5 του στεροειδούς. Τα 5α-7-κετο στεροειδικά παράγωγα που προέκυψαν κατά την αναγωγή του διπλού δεσμού χρησιμοποιήθηκαν αρχικά για τη σύνθεση των στεροειδικών εστέρων της χλωραμβουκίλης και του φαινυλοξικού οξέος και ακολούθως μελετήθηκε η in vivo αντιλευχαιμική τους δράση έναντι της λευχαιμίας Ρ388. Τέλος, η αναγωγή του διπλού δεσμού αποδείχθηκε να έχει αρνητική επίδραση στην αντιλευχαιμική δράση, αφού η συγκριτική μελέτη με τα πρωτότυπα μόρια έδειξε πως οι πολύ δραστικοί Δ5-7-κετο στεροειδικοί εστέρες με την αναγωγή του διπλού δεσμού μετατράπηκαν σε ενώσεις με αμελητέα αντιλευχαιμική δράση. / Recent structure-antileukemic activity studies showed that the steroidal part of complex molecules containing DNA alkylators does not play only the role of the “biological carrier”. New such compounds designed to possess an allylic 7-ketone showed enhanced antileukemic potency compared with derivatives with a simple steroidal skeleton. In order to investigate whether the enhancement of the antileukemic potency is attributed to the introduction of the 7-ketone or to the Δ5-7-keto conjugated steroidal system we decided to reduce the Δ5 double bond. The 5α-7-keto-steroidal skeletons synthesized were tethered to chlorambucil and phenyl acetic acid’s nitrogen mustard and studied against leukemia P338 in vivo. The reduction of the double bond had a negative impact on the antileukemic potency since the comparative study of the novel derivatives showed that a series of very potent Δ5-7-keto-steroidal esters were converted by this modification to compounds with marginally accepted activity.

Είναι ευρέως γνωστό από παλιά ότι οι μουστάρδες του αζώτου όταν είναι συνδεδεμένες μέσω ενός εστερικού δεσμού με ένα στεροειδές μόριο ή με ένα τροποποιημένο στεροειδές, τότε εμφανίζουν μικρότερη τοξικότητα και καλύτερη αντινεοπλασματική δράση. Προκειμένου να επιβεβαιώσουμε το ρόλο του στεροειδικού μορίου στην έκφραση της αντιλευχαιμικής ενεργότητας, επανασυνθέσαμε 16 ανάλογα της μουστάρδας 4-Μe-CABA και τα εξετάσαμε στη λευχαιμία Ρ388 in vivo και σε φυσιολογικά ανθρώπινα λεμφοκύτταρα in vitro. H πλειοψηφεία των εξεταζόμενων ενώσεων εμφάνισε χαμηλή τοξικότητα-χαμηλότερη τοξικότητα από αυτήν της μουστάρδας- ενώ η αντιλευχαιμική δράση αυξήθηκε σημαντικά. Όσον αφορά στις τροποποιήσεις αποδείχτηκε για μια ακόμη φορά ότι η ύπαρξη της ΝΗ-CΟ ομάδας ως εξωκυκλικό αμίδιο συνεισεφέρει σημαντικά στην δράση του μορίου μόνο όμως όταν βρίσκεται σε β-διαμόρφωση. Η μετατροπή του Β αλλά και του D στεροειδικού σκελετού σε λακταμικό ενίσχυσε την αντιλευχαιμική δράση των μορίων. Επίσης τα 7-οξειδωμένα παράγωγα αποδείχτηκαν καλύτερα από τα μη οξειδωμένα ανάλογα. Τα ευρήματα μας υποστηρίζουν ότι το στεροειδικό κομμάτι αυτών των ενώσεων δεν είναι μία απλή βιολογική πλατφόρμα όπως εικαζόταν για χρόνια. / It is commonly known that nitrogen mustards when conjugated with steroids or modified steroids via esteric bond show low toxicity and better antileukemic activity. In order to confirm the role of the steroidal moiety on the expression of anti-leukemic activity we re-synthesized 15 derivatives of the 4-Μe-CABA mustard and tested them on leukaemia P388 in vivo and in normal human lymphocytes in vitro.The majority of the tested compounds showed low toxicity while the measured antileukemic potency was significantly increased.As far as the modifications that were tested, once more it was proved that the existence of the ΝΗ-CΟ moiety when out of the ring as an amidic group contributes significantly to the activity of the molecule only if it is at axial conformation. The lactamization of the B-steroidal ring as well as the lactamization of the D-steroidal ring rendered the molecule more potent. Furthermore the 7-oxidized derivatives proved better than the non-7-oxidized derivatives. Our findings support the notion that the steroidal part of these molecules is not just a simple biological platform as has been speculated for years.

Background: Sex and stress steroids are metabolized to 3a-hydroxy-pregnane-steroid metabolites such as allopregnanolone (Allo) and tetrahydrodeoxycorticosterone (THDOC). Allo and THDOC are neuroactive steroids that are metabolized in the brain and act in brain as potent positive GABAA receptor function modulators. Allo as well as THDOC levels increase during stress. Allo has been associated with a number of symptoms and malfunctions such as impaired memory function and negative mood symptoms in a subgroup of individuals both for animals and humans. Pregnane steroids with 3b-hydroxy-configuration (3b-steroids) have been shown to reduce the Allo enhanced GABA effect. Aims: The aims for the present thesis were to investigate the effect of 3b-steroids on the GABA mediated GABAA receptor function in presence of positive GABAA receptor modulators. Further, the regional variances between the 3b-steroids as well as the mechanism of the effect were studied. Finally, the effect of stress steroid metabolites on the GABAA receptor function was investigated. Results: 3b-OH-5a-pregnane-20-one reduced the Allo enhanced GABA mediated chloride ion uptake into cortical microsacs. The 3b-isomer reduced the efficacy of Allo without shift the concentration response curve. It is therefore suggested that the 3b-isomer has a non-competitive effect. Further, it was shown that the 3b-isomer reduced the Allo effect in a selective way since the 3b-isomer did not interact with other positive modulators or with GABA itself. Five tested 3b-steroids reduced the Allo enhanced GABA mediated chloride ion uptake in cerebral cortex and hippocampus as well as the Allo prolongation on spontaneous inhibitory postsynaptic currents (sIPSCs) in preoptic nucleus. In cerebellum on the other hand the 3b-steroids showed to have weaker or no effect compared to the other tested regions. Interestingly, in absence of Allo, two of the 3b-steroids positively modulated the GABA stimulated GABAA receptor function. In absence of Allo, 5b-pregnane-3b,20(R)-diol increased the desensitization rate of current response. In contrast to the reducing effect on the Allo induced prolongation on sIPSCs, the effect of the 3b-steroid on GABA application, was not altered in presence of Allo. The mechanism of the 3b-steroid is therefore suggested being desensitization dependent in contrast to Allo, which has been suggested to decrease the GABA unbinding rate. In contrast to the enhanced effect of Allo, glucocorticoid metabolites reduced the GABA mediated chloride ion uptake in a concentration dependent way. The results in present thesis indicate that both sex and stress steroid metabolites interact with the GABAA receptor function. The knowledge that diversity of endogenous steroids interact with the GABAA receptor function is of importance for further understanding of different sex and stress steroid related symptoms and syndromes.

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