Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) derivatives possess cancerostatic and anti-infective properties thus making them candidates of possible antibacterial agents. ²-lactam antibiotics are vital weapons for the treatment of bacterial infections, but their existence and effectiveness has been faced with resistance from ²-lactamases. Therefore, the need for new effective antimicrobial drugs is very crucial. In this work, we synthesized in high yields, PBD analogs 1−3, 5 and 7−9 in three to four synthetic steps from commercially available L-proline and isatoic anhydride. MTT Assay was employed to test the in vitro cytotoxicity of PBD analogs 1, 2, 5 and 7 on cancer cell lines including MCF-7, SKBR-3, SKMEL-2, CaCo 2 and Mia Paca. These compounds decreased the cell viability of MCF-7 by roughly 20% however, 1 and 5 had no effect on the SKMEL-2 cell lines. The inhibitory efficacy of these PBDs were also tested against TEM-1 and P99 Serine class A and C ²-lactamases.

Abstract School of Education Växjö University Social Science specialised in Care and Treatment of Juveniles and Substance Abusers C- Essay 10p Titel Benzodiazepines in primary care Authors Taskin Arslan and Mattias Edlund Supervisor Stellan Jeppsson Date March 2006 Number of pages 47 Keyword benzodiazepines, pharmaceutical abuse, tranquillizer, perspective of gender With this essay we have tried to bring up the different causes why there are so many prescriptions of benzodiazepines, the primary cares part in all this and why there are more prescriptions for women than men. The purpose of this study was to increase our knowledge about benzodiazepines, try to find out advantages and disadvantages in case of prescriptions of these preparation and if primary care was aware of these disadvantages in case of prescriptions especially at the matter of prescriptions for women. Some of the questions we asked ourselves were: what kind of risk is connected to benzodiazepines? What kind of responsibility does the doctor have in case of prescriptions of benzodiazepines? How is it that the women constitute the group which receives most prescriptions of benzodiazepines? Our method has been an explorative theoretical study combined with qualitative interviews. In our studies we have found that there is a big awareness about the disadvantages of benzodiazepines prescriptions among the doctors in primary care. And that the conversation between doctor and patient is important for the search of underlying causes. Finally that why women are overrepresented in the matter of benzodiazepine prescription could be due to that women to a greater extent seeks help in non-institutional care than men. / Abstract Institutionen för pedagogik/IKM Växjö universitet Pedagogik med inriktning mot Ungdoms- och missbrukarvård C- Uppsats 10p Titel Bensodiazepins in primary care Författare Taskin Arslan och Mattias Edlund Handledare Stellan Jeppsson Datum Mars 2006 Antal sidor 47 Nyckelord bensodiazepiner, läkemedel, lugnande, genusperspektiv Detta arbete har försökt ta upp de olika orsakerna till varför det föreskrivs så mycket bensodiazepiner, primärvårdens roll i det hela och varför det föreskrivs mer bensodiazepiner till kvinnor än män. Syftet med denna studie var att fördjupa våra kunskaper om bensodiazepiner, försöka ta reda på fördelarna och nackdelarna vid föreskrivning av dessa preparat och om primärvården var medveten om dessa nackdelar speciellt när det gällde föreskrivning till kvinnor. Några av frågorna vi ställde oss var: Vilken risk finns kopplade till bensodiazepiner? Vilken roll respektive vilket ansvar har läkaren vid föreskrivning av bensodiazepiner? Hur kommer det sig att kvinnor utgör den grupp som erhåller flest bensodiazepinförskrivningar? Vår undersökning har varit en explorativ litteraturstudie kombinerad med intervjuer. Det vi har kommit fram till utifrån intervjuerna och litteraturen är att det finns en stor medvetenhet hos läkarna kring riskerna med föreskrivning av bensodiazepiner. Att samtalet mellan läkaren och patienten är viktigt för att utreda de bakomliggande orsakerna och att orsaken till att kvinnor är överrepresenterade vad gäller föreskrivningen av bensodiazepiner kan enligt litteraturen och läkarna vi varit i kontakt med bero på att kvinnor i större utsträckning än män söker hjälp inom vården

<p>Abstract</p><p>School of Education</p><p>Växjö University</p><p>Social Science specialised in Care</p><p>and Treatment of Juveniles and</p><p>Substance Abusers</p><p>C- Essay 10p</p><p>Titel Benzodiazepines in primary care</p><p>Authors Taskin Arslan and Mattias Edlund</p><p>Supervisor Stellan Jeppsson</p><p>Date March 2006</p><p>Number of pages 47</p><p>Keyword benzodiazepines, pharmaceutical abuse, tranquillizer, perspective of gender</p><p>With this essay we have tried to bring up the different causes why there are so many prescriptions of benzodiazepines, the primary cares part in all this and why there are more prescriptions for women than men.</p><p>The purpose of this study was to increase our knowledge about benzodiazepines, try to find out advantages and disadvantages in case of prescriptions of these preparation and if primary care was aware of these disadvantages in case of prescriptions especially at the matter of prescriptions for women.</p><p>Some of the questions we asked ourselves were: what kind of risk is connected to benzodiazepines? What kind of responsibility does the doctor have in case of prescriptions of benzodiazepines? How is it that the women constitute the group which receives most prescriptions of benzodiazepines?</p><p>Our method has been an explorative theoretical study combined with qualitative interviews.</p><p>In our studies we have found that there is a big awareness about the disadvantages of benzodiazepines prescriptions among the doctors in primary care. And that the conversation between doctor and patient is important for the search of underlying causes. Finally that why women are overrepresented in the matter of benzodiazepine prescription could be due to that women to a greater extent seeks help in non-institutional care than men.</p> / <p>Abstract</p><p>Institutionen för pedagogik/IKM</p><p>Växjö universitet</p><p>Pedagogik med inriktning mot</p><p>Ungdoms- och missbrukarvård</p><p>C- Uppsats 10p</p><p>Titel Bensodiazepins in primary care</p><p>Författare Taskin Arslan och Mattias Edlund</p><p>Handledare Stellan Jeppsson</p><p>Datum Mars 2006</p><p>Antal sidor 47</p><p>Nyckelord bensodiazepiner, läkemedel, lugnande, genusperspektiv</p><p>Detta arbete har försökt ta upp de olika orsakerna till varför det föreskrivs så mycket bensodiazepiner, primärvårdens roll i det hela och varför det föreskrivs mer bensodiazepiner till kvinnor än män. Syftet med denna studie var att fördjupa våra kunskaper om bensodiazepiner, försöka ta reda på fördelarna och nackdelarna vid föreskrivning av dessa preparat och om primärvården var medveten om dessa nackdelar speciellt när det gällde föreskrivning till kvinnor. Några av frågorna vi ställde oss var: Vilken risk finns kopplade till bensodiazepiner? Vilken roll respektive vilket ansvar har läkaren vid föreskrivning av bensodiazepiner? Hur kommer det sig att kvinnor utgör den grupp som erhåller flest bensodiazepinförskrivningar? Vår undersökning har varit en explorativ litteraturstudie kombinerad med intervjuer. Det vi har kommit fram till utifrån intervjuerna och litteraturen är att det finns en stor medvetenhet hos läkarna kring riskerna med föreskrivning av bensodiazepiner. Att samtalet mellan läkaren och patienten är viktigt för att utreda de bakomliggande orsakerna och att orsaken till att kvinnor är överrepresenterade vad gäller föreskrivningen av bensodiazepiner kan enligt litteraturen och läkarna vi varit i kontakt med bero på att kvinnor i större utsträckning än män söker hjälp inom vården</p>

Bibliography: leaves 217-238 / xix, 238, [82] leaves : ill ; 31 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Depts. of Psychology and Community Medicine, 1992

Made available in DSpace on 2018-06-04T19:14:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-01-29 / Os Medicamentos Benzodiazepínicos (BZD) são caracterizados como uma das classes de medicamentos mais consumidas no mundo e possuem significativo potencial de risco para abuso e dependência. No Brasil, diversos estudos demonstram o uso destes medicamentos em situações que não se caracterizam como de “uso racional”. O objetivo desta pesquisa foi caracterizar o uso e o usuário de medicamentos psicoativos benzodiazepínicos no serviço público de saúde na população da região de Cidade Tiradentes do município de São Paulo. Para atingir seu objetivo se utilizou de abordagem qualitativa baseada na metodologia de análise de conteúdo. O estudo foi complementado por uma análise quantitativa descritiva. Entrevistas semiestruturadas foram aplicadas a prescritores e usuários de BZD. A pesquisa foi autorizada pelo Comitê de Ética e Pesquisa da Universidade Federal de São Paulo e pelo Comitê de Ética e Pesquisa da Secretaria Municipal de Saúde da cidade de São Paulo. O BZD mais dispensado foi o Clonazepam 2mg e o total destes medicamentos dispensados no período de três meses somam 2,50 DDD/mil habitantes/dia. A maioria dos usuários foi do sexo feminino e acima dos 40 anos. Os prescritores classificaram o uso como “não racional” e identificaram uso abusivo e dependência no uso cotidiano. Os usuários declararam utilizar os BZD por vários anos, desconhecem as implicações do uso crônico e até informações básicas como indicação e duração do tratamento. / The Medicines Benzodiazepines (BZD) are characterized as one of the classes of drugs most consumed in the world and have significant potential risk for abuse and dependence. In Brazil, several studies have shown the use of these drugs in situations that are not characterized as rational use. The aim of this study was to characterize the use and drug user psychoactive benzodiazepines in the public health service in the population of Cidade Tiradentes region of São Paulo. To achieve its goal was used a qualitative approach based on the content analysis methodology. The study was completed by a quantitative descriptive analysis. Semi-structured interviews were applied to prescribers and BZD users. The study was approved by the Ethics and Research Committee of the Federal University of São Paulo and by the Research Ethics Committee of the Municipal Health Secretariat of São Paulo. The most dispensed BZD was Clonazepam 2mg and the total of these medications dispensed in three months added 2.50 DDD / inhabitants / day. Most users were female and over 40 years. Prescribers classified use as not rational and identified abuse and dependence in everyday use. Users reported using the BZD for several years, unaware of the implications of chronic use and even basic information such as indication and duration of treatment. / BV UNIFESP: Teses e dissertações

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The adulteration of phytotherapic formulations has been a common practice in many countries, since there is not an specific legislation for the control of the manufacturing and commercialization of the so called natural medicaments . In this context, the existence of analytical methodologies, which alllow the identification and quantification of possible pharmaceuticals as adulterants in these formulations is very important in the toxicological analysis. Since the possibilitiy of adulteration is very broad in terms of compound classes, the analytical methods have to be very selective and sensitve for the identification os compound classes and/or individual compounds. In this work, a voltammetric method was developed and validated for the selective determination of pharmaceuticals from the class of 1,4-benzodiazepines (ansiolytics) and diethylpropion (anorexics). In order to investigate the possible interference of other electroactive drugs (possible adulterants in phytotherapic formulations) at the mercury electrode, synthetic mixtures containing different concentrations of 1,4-benzodiazepines, diethylpropion and interferents fluoxetine, sibutramine and metformin were analyzed. The parameters of the voltammetric analysis, such as pH, potential and time of deposition, were optimized aiming a voltammetric measurement with high selectivity and sensitivity. The validated method was applied for the determination of the adulterants in phytotherapic formulations used in the treatment of obesity, which have been commercialized as natural medicaments by Brazilian pharmacies. Four different phytotherapic formulations were found to be contaminated by 1,4-benzodiazepines in concentration ranging from 0,056 to 0,270 mg/g. Recovery experiments for 1,4-benzodiazepines and diethylpropion were carried out in the formulations, which gave recovery values higher than 90% for all the analyzed adulterants. The developed and validated method presented high sensitivity, selectivity, analytical precision and short analysis time. Therefore, the method is very usefull as an analytical tool for the control and fiscalization of the adulteration of phytotherapic formulations. / A adulteração de formulações fitoterápicas tem sido uma prática recorrente em todo o mundo, tendo em vista o fato de que ainda não existe uma legislação específica de controle da manipulação e comercialização dos chamados medicamentos naturais . Neste sentido, a existência de metodologias analíticas que possibilitem a identificação e a quantificação de possíveis fármacos como adulterantes nestas formulações é de extrema importância na análise toxicológica. Como a possibilidade de adulteração é relativamente ampla em termos de classes de compostos, os métodos analíticos requerem principalmente boa seletividade e sensibilidade na identificação de classes e/ou compostos individuais. Neste trabalho, um método voltamétrico foi desenvolvido e validado para a determinação seletiva de fármacos da classe dos 1,4-benzodiazepínicos (ansiolíticos) e da dietilpropiona (anorexígeno). Para avaliar uma possível interferência na determinação destes fármacos causada por outros fármacos eletroativos (possíveis adulterantes em formulações fitoterápicas) no eletrodo de mercúrio, misturas sintéticas com diferentes concentrações dos 1,4-benzodiazepínicos, dietilpropiona e os interferentes fluoxetina, femproporex, sibutramina e metformina foram analisadas. Os parâmetros da análise voltamétrica pH, potencial e tempo de deposição foram otimizados, visando uma medida voltamétrica com alto grau de seletividade e sensibilidade. O método validado para a determinação de 1,4-benzodiazepínicos e dietilpropiona foi empregado na análise de formulações fitoterápicas utilizadas no tratamento da obesidade, as quais são comercializadas como medicamentos naturais por farmácias de manipulação brasileiras. Quatro diferentes formulações fitoterápicas analisadas acusaram a presença de 1,4-benzodiazepínicos como adulterantes em concentrações entre 0,056 e 0,270 mg/g. Ensaios de recuperação para os 1,4-benzodiazepínicos e dietilpropiona foram realizados nas formulações, obtendo-se recuperações acima de 90% para todas as espécies de adulterantes analisadas. O método desenvolvido e validado apresentou alta sensibilidade, seletividade, precisão analítica, baixo custo e análises rápidas, comprovando a aplicabilidade do mesmo como uma alternativa para o controle e fiscalização da adulteração em formulações fitoterápicas.

Orientador: Maria de Fátima Araújo / Banca: Abilio da Costa Rosa / Banca: Ana Raquel Rosas Torres / Banca: Daniela Sacramento Zanini / Banca: Sílvio Yasui / Resumo: No Brasil, existe um alto consumo de medicamentos benzodiazepínicos (BZD), maior entre as mulheres, principalmente, idosas. A dependência ao BZD ocorre com o apoio do sistema de saúde, que permite a prescrição e repetição de receitas por tempo prolongado. Contribuem para esta prática: a hegemonia do discurso biomédico sem problematizar a categoria gênero e demais indicadores sociais; a falta de uma legislação e fiscalização mais eficazes, sobre o comércio e dispensação de BZD. Percebe-se que as práticas de atenção à saúde reafirmam uma objetivação do corpo feminino, contribuindo para a medicalização das relações de gênero. Essa pesquisa objetiva investigar a interface saúde mental e gênero, dentro das práticas de cuidado das equipes da estratégia saúde da família (ESF), com foco, na utilização de ansiolíticos. Esse estudo utilizou a pesquisa-ação, contemplando dois momentos: uma aproximação e diagnóstico do campo, utilizando metodologia quantitativa e, logo após, uma proposta de intervenção com metodologia qualitativa. Transversaliza esse estudo, a perspectiva de gênero que tenta compreender como as relações e dinâmicas sociais são capazes de atualizar-se, para promover uma organização social da diferença sexual. A pesquisa foi realizada em seis equipes da Estratégia Saúde da Família (ESF) de duas cidades brasileiras: Assis e Goiânia. No primeiro momento, de diagnóstico, foram avaliados todos os prontuários de usuários e usuárias dos ansiolíticos Diazepam e Clonazepam, das seis ESF selecionadas, aplicando um questionário que avaliava questões relacionadas ao uso de BZD, totalizando 132 participantes / Abstract: In Brazil, there is a high consumption of Benzodiazepine-based medicine (BZD), greater among women, mostly elderly ones. Dependence on BZD happens with the support of the healthcare system, which allows repeated prescriptions over a long period of time. The following also contribute to this practice: the hegemony of the biomedical speech without problematizing the gender category and other social indicators; the lack of a more effective legislation and control of the commerce and dispense of BZD. It is noticed that the healthcare practices reassure an objectivation of the female body, contributing to medicalization of the gender relations. This research aims to investigate the interface between mental health and gender within the practices of the healthcare teams of the Family Health Strategy (FHS), with a focus on anxiolytics. This study made use of action research, considering two moments: a field approach and diagnosis using quantitative methodology and then an intervention proposal with qualitative methodology. This study is transversed by a gender perspective that tries to understand how the social relationships and dynamics are capable of updating themselves in order to promote a social organization of sexual difference. The research was accomplished in six teams of the Family Health Strategy (FHS) from two Brazilian cities: Assis and Goiania. At the first stage, that of diagnosis, all the anxiolytic Diazepam and Clonazepam users were evaluated, from the six FHS selected, by means of a questionnaire that assesses issues related to the use of BZD, in a total of 132 participants / Doutor

Abstract The aim of this thesis was to explore the associations between the use of nervous system medications and suicidal ideation and behaviour in various different diagnostic groups in a large population-based cohort. Information on prescribed antipsychotic, antidepressant, benzodiazepine and antiepileptic medications within the Northern Finland Birth Cohort 1966 was collected from the register of the Social Insurance Institution of Finland and from a postal questionnaire sent to all cohort members in 1997. The presence of suicidal ideation and depression and anxiety symptoms was assessed via the Hopkins Symptom Checklist-25 questionnaire in 1997. Data on suicides were collected from the cause-of-death statistics and on suicide attempts from the Finnish Care Register for Health Care in a 15-year follow up. The use of antipsychotic, antidepressant, or benzodiazepine medication was associated with increased suicidal ideation, suicide attempts, and suicides. Antiepileptic medication was not associated with increased suicidality. The polypharmacy of nervous system medications was associated with increased suicidality. All nervous system medications were associated with increased severity of depression and anxiety symptoms. When depression and anxiety symptoms were taken into account, most of the associations between medication and suicidal ideation were statistically non-significant. Regarding specific groups, among those who did not have psychosis, high doses of antipsychotic medication correlated particularly with increased suicidal ideation even when other symptoms of depression and anxiety were taken into account. Among those with insomnia, the use of antidepressant medication associated with increased suicidal ideation also when other symptoms were taken into account. Although nervous system medication is associated with increased suicidal ideation, the association with other symptoms is also strong, and therefore it could not be stated that medication associates specifically with suicidal ideation. However, certain groups, i.e., non-psychotic subjects with high doses of antipsychotic medication, or subjects with insomnia and using antidepressant medication, should be closely monitored as they could be more vulnerable to suicidal ideation. / Tiivistelmä Tämän väitöstutkimuksen tarkoituksena oli tutkia hermostoon vaikuttavien lääkkeiden, lähinnä psykoosilääkkeiden, masennuslääkkeiden, bentsodiatsepiinien sekä epilepsialääkkeiden, yhteyttä itsetuhoisiin ajatuksiin, itsemurhayrityksiin ja itsemurhiin. Aihetta tutkittiin eri diagnoosiluokissa suuressa väestöaineistossa, Pohjois-Suomen vuoden 1966 syntymäkohortissa. Tieto tutkimushenkilöiden lääkkeenkäytöstä vuodelta 1997 kerättiin Kelan lääkeostorekisteristä sekä postikyselyn avulla. Itsetuhoisten ajatusten ja muiden masennus- ja ahdistusoireiden vakavuutta mitattiin Hopkins Symptom Checklist-25 -kyselyn avulla vuonna 1997. Tieto itsemurhista kerättiin 15 vuoden seurannassa kuolinsyyrekisteristä ja tieto itsemurhayrityksistä hoitoilmoitusrekisteristä. Psykoosilääkkeiden, masennuslääkkeiden ja bentsodiatsepiinien käyttö oli yhteydessä lisääntyneisiin itsetuhoisiin ajatuksiin, itsemurhayrityksiin ja itsemurhiin. Epilepsialääkkeet eivät liittyneet itsetuhoisuuteen. Usean hermostoon vaikuttavan lääkkeen yhtäaikainen käyttö oli yhteydessä lisääntyneeseen itsetuhoisuuteen. Kaikki hermostoon vaikuttavat lääkkeet liittyivät lisääntyneisiin masennus- ja ahdistusoireisiin. Kun lääkityksen yhteys masennus- ja ahdistusoireisiin otettiin huomioon, lääkkeet eivät olleet erityisesti yhteydessä itsetuhoisiin ajatuksiin. Diagnostisten ryhmien välillä ei ollut eroa hermostoon vaikuttavien lääkkeiden ja itsemurhayritysten tai itsemurhien välisessä yhteydessä. Henkilöillä, joilla ei ole psykoosia, suuremmat psykoosilääkeannokset olivat yhteydessä itsetuhoisten ajatusten vakavuuteen kun muiden masennus- ja ahdistusoireiden vakavuus otettiin huomioon. Unettomuudesta kärsivillä henkilöillä masennuslääkkeen käyttö oli liittyi lisääntyneisiin itsetuhoisiin ajatuksiin kun muut oireet huomioitiin. Hermostoon vaikuttavat lääkkeet ovat yhteydessä lisääntyneisiin itsetuhoisiin ajatuksiin, mutta ne ovat myös vahvasti yhteydessä muihin masennus- ja ahdistusoireisiin. Tietyt henkilöt voivat kuitenkin olla erityisen herkkiä nimenomaan itsetuhoisille ajatuksille, ja heitä tulisi seurata erityisen tiiviisti. Tällaisia ovat henkilöt, joilla ei ole psykoosia, mutta jotka käyttävät suuria psykoosilääkeannoksia, sekä vakavasta unettomuudesta kärsivät henkilöt, jotka käyttävät masennuslääkettä.

Abstract Antipsychotic medication forms the basis of the long-term, even lifelong treatment of schizophrenia. Antipsychotic polypharmacy and adjunctive psychiatric medications are also common treatment strategies. The long-term effects of psychiatric medication, especially on cognition in schizophrenia, are largely unknown. Cognitive impairment is a central, persisting symptomatic feature during the lifespan course of schizophrenia and a key predictor of functional outcome. This naturalistic study aimed to analyse how the lifetime exposure to antipsychotic, benzodiazepine and antidepressant medications, and lifetime trends in antipsychotic use, were associated with cognition in early midlife in schizophrenia. Non-psychotic controls were included as a reference group of normative cognitive performance. The study samples consisted of 40–60 subjects with schizophrenia and 73–191 non-psychotic controls from the Northern Finland Birth Cohort 1966. Data on the lifetime use of medications were collected from medical records, registers and interviews and connected with information from extensive psychiatric and neurocognitive assessments at the ages of 34 and 43 years. Higher cumulative lifetime exposure to antipsychotics was associated with poorer verbal learning and memory at 34 years of age, a decline in verbal learning and memory between the ages of 34 and 43 years and poorer global cognition at the age of 43 years in schizophrenia. A relatively long antipsychotic-free period before the cognitive assessment was associated with better global cognition at 43 years of age. Other lifetime trends in antipsychotic use, antipsychotic polypharmacy or cumulative benzodiazepine or antidepressant exposures were not associated with global cognition. This naturalistic study was the first to report an association between higher cumulative lifetime antipsychotic exposure and poorer cognition in early midlife in schizophrenia, which was not likely confounded by the use of other psychiatric medications or illness-related factors. Though residual confounding is still possible, these results suggest that high-dose long-term antipsychotic treatment may have some influence on the clinical course of schizophrenia, possibly by attenuating cognitive recovery. More research on the long-term effects of psychiatric medications is needed to develop the safe and effective treatment of schizophrenia. / Tiivistelmä Psykoosilääkitys on skitsofrenian pitkäaikaisen, jopa elinikäisen hoidon perusta. Useiden psykoosilääkkeiden yhtäaikaiskäyttö ja muiden psyykenlääkkeiden oheiskäyttö ovat yleisiä hoitostrategioita. Psyykenlääkkeiden pitkäaikaisvaikutuksia etenkin kognitioon skitsofreniassa tunnetaan huonosti. Kognitiiviset puutokset ovat keskeinen, elinaikaisesti pysyvä skitsofrenian oirepiirre ja merkittävimpiä ennustetekijöitä. Tämän naturalistisen tutkimuksen tavoite oli analysoida elinaikaisen psykoosi-, bentsodiatsepiini- ja masennuslääkealtistuksen sekä elinaikaisten psykoosilääkkeiden käytön trendien yhteyttä kognitioon varhaisessa keski-iässä skitsofreniassa. Ei-psykoottiset verrokit toimivat normatiivisen kognitiivisen suorituskyvyn vertailuryhmänä. Tutkimusaineisto koostui Pohjois-Suomen vuoden 1966 syntymäkohorttiin kuuluvista 40 ja 60 henkilöstä, joilla oli skitsofrenia, sekä 73 ja 191 ei-psykoottisesta verrokista. Tiedot psyykenlääkkeiden elinaikaiskäytöstä kerättiin sairauskertomuksista, rekistereistä ja haastatteluista, ja ne yhdistettiin 34 ja 43 vuoden iässä tehtyihin laajoihin psykiatrisiin ja neuropsykologisiin tutkimuksiin. Korkeampi kumulatiivinen elinaikainen psykoosilääkealtistus oli yhteydessä heikompaan kielelliseen muisti- ja oppimissuoriutumiseen 34-vuotiaana ja sen suurempaan laskuun 34 ja 43 ikävuoden välillä sekä heikompaan kognitioon 43-vuotiaana skitsofreniassa. Suhteellisen pitkä psykoosilääketauko ennen neuropsykologista tutkimusta oli yhteydessä parempaan kognitioon 43-vuotiaana. Muut elinaikaisen psykoosilääkityksen käytön trendit, psykoosilääkkeiden yhtäaikaiskäyttö tai elinaikainen kumulatiivinen bentsodiatsepiini- tai masennuslääkealtistus eivät olleet yhteydessä kognitioon. Tämä naturalistinen tutkimus kuvasi ensimmäisenä yhteyden suuremman kumulatiivisen elinaikaisen psykoosilääkealtistuksen ja heikomman kognition välillä varhaisessa keski-iässä skitsofreniassa. Muiden psyykenlääkkeiden käyttö tai sairauteen liittyvät tekijät eivät näyttäneet sekoittavan tätä yhteyttä. Vaikka on mahdollista, että kaikkia sekoittavia tekijöitä ei pystytty huomioimaan, tulosten perusteella korkea-annoksinen, pitkäaikainen psykoosilääkitys saattaa vaikuttaa skitsofrenian taudinkulkuun heikentämällä kognitiivista toipumista. Lisätutkimusta psyykenlääkityksen pitkäaikaisvaikutuksista tarvitaan skitsofrenian turvallisen ja tehokkaan hoidon kehittämiseksi.

Environmental pollution by pharmaceuticals is an issue of concern that is currently attracting attention around the world. Although environmental effects of pharmaceutical contaminants are not yet well documented, studies have shown that these substances may have the potential to disrupt the biotic component of an ecosystem. Particularly worrisome contaminants are the neuroactive pharmaceuticals which have the potentiality to induce behavioral modifications in non-target species. In the present study, I examined the effects of a benzodiazepine anxiolytic pharmaceutical (oxazepam) on the behavior of Atlantic salmon (Salmo salar) juveniles (fry). The hypothesis of this study was that oxazepam reduces the anxiety-like behavior of the Atlantic salmon juveniles. To test the hypothesis and assess the impact of oxazepam exposure on Atlantic salmons fry behavior, two different concentrations of this drug; a low-level (1.9 ug L-1) and a high-level concentration (1000 ug L-1) were used. Exposures lasted for 48 hours and afterwards, the fish were recorded to evaluate their behavioral responses. The results of this study reveal that oxazepam in a high concentration (1000 ug L-1 ) alters specific behavioral endpoints related to the fitness (feeding/predator avoidance) of Atlantic salmons fry. Individuals exposed to the high oxazepam concentration exhibited significant lower average speed and acceleration as well as they traveled a shorter mean distance compared to the unexposed (control) individuals. These findings confirm the hypothesis and show that psychotropic pharmaceutical contaminants modify animal behaviors, which can ultimately lead to ecological consequences. However, the concentration that generated behavioral effects in this study was three magnitudes higher than concentrations measured in the environment and thus, should not be viewed representative for oxazepam contaminated ecosystems.