Abstract Each year approximately 11,000 induced abortions are performed in Finland, the majority of these women being younger than 25 years of age. Medical abortion with the antiprogestin mifepristone and the prostaglandin analogue misoprostol is increasingly being used instead of surgical method (dilatation of cervix and uterine evacuation with instruments). Similarly, miscarriages can be treated with medical or surgical management. Still, clinical outcomes of the medical treatment of miscarriage are not well established, and various different regimens exist. The aim of this study was to investigate the frequency and risk factors of repeat abortions and immediate post-abortal complications, focusing especially on the impact of the method of abortion. National health registries were used as a data source. Another part of the study was aimed at comparing the efficacy, acceptability and cost-effectiveness of the medical and surgical treatment of miscarriage. In national cohort, the risk of repeat abortion was associated with sociodemographic characteristics (parity, previous abortion, low socioeconomic status, being unmarried but cohabiting or single), but not with the method of abortion. The risk of repeat termination of pregnancy decreased with age, among women living in rural area, and when intrauterine devices or sterilization were planned for future contraception. The overall incidence of adverse events was 4-fold greater in the medical compared to the surgical abortion cohort. Hemorrhage and incomplete abortion were more common following medical abortion, but the incidence of infections did not differ. Medical and surgical treatment of miscarriage were compared in a randomized setting; the efficacy of the treatment did not differ. Medically treated patients were less satisfied with the treatment and had experienced more pain. In the cost analysis, the primary costs of the surgical treatment were higher, but more unexpected events and complications increased the secondary costs in the medical group. In summary, medical abortion offered a good alternative to surgical method without increasing the risk of repeat abortions, but with an increased risk of short-term adverse events. The medical method was efficient in treating miscarriages, and the majority of women were satisfied with the treatment. Neither of the methods was economically superior in treating miscarriage.

Einleitung: Nach einer kontrovers diskutierten Einführung von Mifepriston im Jahre 1999 in Deutschland weisen die niedrigen Anwendungszahlen auf eine zögerliche Etablierung hin. Aufgrund der aktiven Einbeziehung der Frau in die Durchführung des Schwangerschaftsabbruches wird oft eine erschwerte emotionale Verarbeitung vermutet. Wir untersuchten die psychische Belastung vor und nach medikamentösem und chirurgischem Abbruch. Methoden: 147 Frauen mit gewähltem medikamentösen und 72 Frauen mit chirurgischem Abbruch wurden vor und vier Wochen nach dem Eingriff befragt. Neben demographischen Aspekten, Beweggründen, Kriterien der Methodenauswahl und medizinischen Details wurden die deutsche Fassung der Hospital Anxiety and Depression Scale (HADS) und der Impact of Event Scale (IES) verwendet. Ergebnisse: Die demographischen Angaben zeigten keine Unterschiede zwischen den Anwenderinnen beider Methoden. Bei einem Vergleich der Ergebnisse der HADS vor und vier Wochen nach dem Abbruch zeigte sich ein signifikanter Abfall der Werte für Angst und Depression bei beiden Methoden. Die Anwenderinnen von Mifepriston wiesen jedoch deutlich seltener erhöhte Angstwerte vor dem Schwangerschaftsabbruch auf. Vier Wochen später zeigten die Werte für Angst und Depression keine signifikanten Unterschiede zwischen beiden Verfahren mehr. Auf den Skalen der IES wurde ein geringeres Ausmaß von erlebter Intrusion und Vermeidungshaltung bei den Frauen der medikamentösen Methode gefunden. Im Vergleich deutlich stärker waren die erlebten Blutungen, Schmerzen und Nebenwirkungen bei der Anwendung von Mifepriston. Dieses hatte jedoch weder einen negativen Einfluss auf die psychische Verarbeitung des Ereignisses noch auf die hohe Akzeptanz der Methode. Eine überwältigende Mehrheit der Frauen beider Methoden schätzte es als außerordentlich wichtig ein, zwischen verschiedenen Methoden wählen zu können. In einer hypothetischen Zukunftssituation würden sich 80,3 % der Frauen nach medikamentöser Methode und 62,9 % der Frauen nach chirurgischer Methode wieder für die gleiche Methode entscheiden. Schlussfolgerung: Unsere Untersuchung belegt die in anderen Studien allgemein geteilte Auffassung, dass die Beendigung einer ungewollten Schwangerschaft unabhängig von der durch die Frau gewählten Methode eine positive erste Konfliktlösung bedeutet. Die positiven Ergebnisse der psychischen Verarbeitung und die hohe Zufriedenheit der Anwenderinnen unterstreicht die Notwendigkeit einer Aufrechterhaltung der Auswahlmöglichkeit zwischen verschiedenen Methoden zur Schwangerschaftsbeendigung und einer verbesserten Zugänglichkeit zur medikamentösen Methode mit Mifepriston in Deutschland. / Introduction: After a controversial introduction of medical abortion with mifepristone in 1999 this method is still not widely available in Germany. Because of the active participatory role of the women many doctors fear a higher rate of psychological sequelae after an abortion with mifepristone. In our study we compared the coping process of women who chose the medical procedure to terminate an unwanted pregnancy with others who opted for surgical abortion. Methodology: Women were asked before and four weeks after the procedure to complete a questionnaire covering demographic data, motivation, medical details and social support. Additionally, the women completed the German Version of the Hospital Anxiety and Depression Scale (HADS) and the Impact of Event Scale (IES). The following evaluation compares the data of 147 women who chose medical abortion with the results of 72 women who preferred a surgical abortion. Results: No significant differences were found for the demographic background of the women using the two different methods. Comparing data before and a month after the abortion, our study shows a significant decline of both anxiety and depression for both methods. Women using the abortion with mifepristone showed significantly lower entrance levels on the anxiety subscale than the surgical group. There were no significant differences in post-abortion anxiety and depression levels. For the IES, women choosing medical abortion scored significantly lower on the intrusion and avoidance subscales than the women opting for surgical abortion. Women using mifepristone experienced significantly more bleeding, pain and other side effects. However, these side effects did neither show a negative influence on the psychological coping nor on the high acceptability of mifepristone. An overwhelming majority of women in both groups evaluated choosing between different abortion methods as being highly important to them. 80,3 % of the women after medical abortion with mifepristone and 62,9 % of the women after surgical abortion would chose the same method again. Conclusions: Our study supports the consensus view that termination of an unwanted pregnancy is a positive first solution to the conflict, regardless of the chosen method. The positive outcome and high satisfaction levels among the participants illustrate the importance of an ongoing and improved accessibility of medical abortion for women in Germany.

Glucocorticoid hormones modulate acute and chronic behavioral and molecular responses to drugs of abuse including psychostimulants and opioids. Acute ethanol activates the hypothalamic pituitary adrenal (HPA) axis causing the release of adrenal glucocorticoid hormones, but following chronic ethanol the HPA axis is dysregulated in both humans and rodents. Thus, there is growing evidence that glucocorticoids might also modulate behavioral and molecular responses to ethanol. Previous microarray studies in the Miles’ laboratory have shown that the well-known glucocorticoid responsive gene, Serum and Glucocorticoid-regulated Kinase 1, Sgk1, is prominently up regulated by acute ethanol (2 g/kg) in the prefrontal cortex (PFC) of DBA/2J mice. Functionally, Sgk1 is an important focal point of intracellular signaling cross-talk through which the cell surface receptors, nuclear receptors, and cellular stress pathways converge to control many cellular processes including receptor or ion channel trafficking, cell proliferation and/or apoptotic responses. In the aforementioned microarray studies, Sgk1 was accompanied by a highly correlated group of genes, many of which are also known to respond to glucocorticoids. This suggests that stress-related signaling events might play an important role in ethanol regulation of the Sgk1 gene network. Prior work by others showed that Sgk1 plays an important role modulating synaptic plasticity occurring in memory. Based on these findings, it is hypothesized that glucocorticoids and glucocorticoid responsive genes are responsible for modulating acute and chronic cellular and behavioral responses to ethanol including locomotor activation and ethanol sensitization. In particular, because Sgk1 is regulated by ethanol, has a well-established role in learning and memory and is responsive to glucocorticoid signaling we hypothesize that Sgk1 is involved in modulating acute and chronic cellular and behavioral responses to ethanol including ethanol sensitization. Our results indicate that the induction of glucocorticoid responsive genes may play a role in regulating acute behavioral and cellular responses to ethanol. Adrenalectomized (ADX) and mifepristone (RU-486) both impaired acute ethanol (2 g/kg) induced locomotor activation in DBA/2J mice without affecting basal locomotor activity. ADX mice showed microarray gene expression changes in the PFC that significantly overlapped with acute ethanol-responsive gene sets derived by our prior microarray studies. Additionally, acute ethanol regulates Sgk1 transcription via glucocorticoid receptor binding to the Sgk1 promoter. Furthermore, increases in Sgk1 may occur to compensate for decreases in SGK1 protein and phosphorylation of SGK1 and its well-known target N-myc downstream-regulated gene 1 (NDRG1) is significantly increased 15 minutes following ethanol administration. Finally, Sgk1 intensifies and prolongs the expression phase of sensitization in D2 mice. Our studies suggest that ethanol’s activation of adrenal glucocorticoid release and subsequent glucocorticoid receptor activation may partially modulate ethanol’s acute locomotor activation in male D2 mice. Furthermore, adrenal glucocorticoid basal tone regulates PFC gene expression. A significant set of acute ethanol-responsive genes are regulated by adrenal glucocorticoid basal tone suggesting that glucocorticoid regulated PFC gene expression may be an important factor modulating acute behavioral responses to ethanol. Sgk1 is acutely regulated following ethanol administration by the glucocorticoid receptor binding to the Sgk1 promoter. Altogether, these results suggest a critical role for the hypothalamic pituitary adrenal axis and Sgk1 in regulating the acute and chronic cellular and behavioral responses to ethanol.

De två läkemedel som administreras vid medicinsk abort i Sverige idag består av de aktiva substanserna mifepriston respektive misoprostol. Behandlingskuren bygger på effekter hos de endogena ämnena progesteron och prostaglandiner. I denna studie beskrivs fysiologiska processer under graviditeten med avseende på progesteron och prostaglandiner samt vid medicinsk abort med avseende på mifepriston och misoprostol. Valet av fokus på fysiologiska processer speglar biologilärarens didaktiska uppgift i att undervisa om hur människokroppen fungerar och dess interaktion med läkemedel. Slutligen presenteras och diskuteras även möjligheter och svårigheter med undervisning om abort inom ramen för högstadie- och gymnasieskolans biologiundervisning. / The drugs administrated to cause medical abortion consist of one tablet with the active substance mifepristone and one with the active substance misoprostol. The regime is based on effects of the endogenic substances progesterone and prostaglandins. In this study, physiological processes in pregnancy regarding progesterone and prostaglandins are described, as well as the physiological processes in medical abortion with respect to mifepristone and misoprostol. The focus on physiological processes relates to the mission of the biology teacher to explain how the human body works and interacts with medical drugs. Finally, opportunities and difficulties with instructions on abortion in secondary and upper secondary school biology are presented and discussed.

17 beta-Hydroxy-11 beta(4-dimethylaminophenyl)-17 alpha-(1-propynyl)estra-4, 9-dien-3-one (RU486) inhibited the in vitro development of different stages of mouse preimplantation embryos under study. Two-celled embryos, morulae, and early blastocysts were obtained from B6D2F1 mice. The embryos were grown in Ham F-10 nutrient mixture (with glutamine) supplemented with sodium bicarbonate (2.1 g/L), calcium lactate (282 mg/L), and bovine serum albumin (fraction V, 3 mg/mL) at 37 degrees C in a humidified incubator supplied with 5% CO2 in air. RU486 was added to the culture medium at concentrations of 1, 5, 10, and 20 micrograms/mL. Culture medium with 0.05% ethanol served as the control. In vitro growth of embryos was assessed by the following criteria: (i) two-celled stage embryo development to blastocyst stage after 72 h, (ii) morula stage grown to blastocyst stage after 24 h, and (iii) early blastocyst stage development to hatching blastocyst after 12 h, in culture. RU486 inhibited the in vitro development of two-celled embryos, morulae, and early blastocysts at concentrations of 5, 10, and 20 micrograms/mL culture medium (p less than 0.001). The inhibitory effect of RU486 at these concentrations on the development of all the stages of embryos under study was irreversible. However, RU486 did not affect embryo development at 1 microgram/mL culture medium. The study indicates the direct adverse effect of RU486 at 5 micrograms/mL and higher concentrations in culture medium on the development of mouse preimplantation embryos in vitro, and it encourages its further investigation as a postcoital contraceptive in animal models and humans.

Synapses can be altered due to experiences in a process called synaptic plasticity, which causes memory formations. Synapses can be strengthened through methods known as long-term potentiation (LTP) or weakened through long-term depression (LTD). Stresses can cause changes by altering synapses through either LTP or LTD. Rats were used to study the effects of post-traumatic stress disorder (PTSD)-like symptoms and a prophylactic treatment using pharmaceuticals. The first model used was the single prolonged stress (SPS) with two weeks of chronic light, which was not as effective for causing changes in synaptic plasticity. The second model, seven days of social defeat (SD) with two weeks of chronic light was more effective at inducing PTSD-like behavior symptoms and causing changes in LTP levels in the ventral hippocampus, amygdala, and prefrontal cortex between stressed and non-stressed rats. For the prophylactic treatment, propranolol and mifepristone were administered one week prior to and throughout the two weeks of the social defeat protocol. The drugs were able to prevent the changes due to stress on LTP in the three aforementioned brain regions, but did not change the anxious behavior of the rats. An enzyme-linked immunosorbent assay (ELISA) was used to determine corticosterone and norepinephrine levels between the different groups of rats. No significant differences were detected between SD and control rats, but SD injected rats were different from controls indicating that the injections were causing added stress. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was used to detect changes in the adrenergic, corticoid, AMPA, and NMDA receptors. There were a few significant changes to some of the targets indicating that the stress protocol and drugs were having an effect on the mRNA expression. Propranolol and mifepristone could possibly be used as a prophylactic treatment for traumatic stress. In a separate study, techniques were used to determine the negative effects chronic stress (non-PTSD-like) has on synaptic plasticity in the dorsal hippocampus and to show how exercise was able to mitigate some of those negative stress effects. Electrophysiology showed differences in LTP between four groups of mice: sedentary no stress (SNS), sedentary with stress (SWS), exercise with stress (EWS), and exercise no stress (ENS). SWS had the lowest amount of LTP, whereas ENS had the highest. SNS and EWS had similar levels of LTP, which were in between the SWS and ENS groups. Corticosterone blood levels measured by an ELISA showed significant increases in the stressed groups compared to the non-stressed groups. The radial arm maze showed that both groups of exercise mice made fewer reference memory errors the second week of testing compared to the sedentary groups. RT-qPCR determined that brain-derived neurotrophic factor (BDNF) and corticoid and dopamine 5 receptors were likely causing some of the memory changes.

Synapses can be altered due to experiences in a process called synaptic plasticity, which causes memory formations. Synapses can be strengthened through methods known as long-term potentiation (LTP) or weakened through long-term depression (LTD). Stresses can cause changes by altering synapses through either LTP or LTD. Rats were used to study the effects of post-traumatic stress disorder (PTSD)-like symptoms and a prophylactic treatment using pharmaceuticals. The first model used was the single prolonged stress (SPS) with two weeks of chronic light, which was not as effective for causing changes in synaptic plasticity. The second model, seven days of social defeat (SD) with two weeks of chronic light was more effective at inducing PTSD-like behavior symptoms and causing changes in LTP levels in the ventral hippocampus, amygdala, and prefrontal cortex between stressed and non-stressed rats. For the prophylactic treatment, propranolol and mifepristone were administered one week prior to and throughout the two weeks of the social defeat protocol. The drugs were able to prevent the changes due to stress on LTP in the three aforementioned brain regions, but did not change the anxious behavior of the rats. An enzyme-linked immunosorbent assay (ELISA) was used to determine corticosterone and norepinephrine levels between the different groups of rats. No significant differences were detected between SD and control rats, but SD injected rats were different from controls indicating that the injections were causing added stress. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was used to detect changes in the adrenergic, corticoid, AMPA, and NMDA receptors. There were a few significant changes to some of the targets indicating that the stress protocol and drugs were having an effect on the mRNA expression. Propranolol and mifepristone could possibly be used as a prophylactic treatment for traumatic stress. In a separate study, techniques were used to determine the negative effects chronic stress (non-PTSD-like) has on synaptic plasticity in the dorsal hippocampus and to show how exercise was able to mitigate some of those negative stress effects. Electrophysiology showed differences in LTP between four groups of mice: sedentary no stress (SNS), sedentary with stress (SWS), exercise with stress (EWS), and exercise no stress (ENS). SWS had the lowest amount of LTP, whereas ENS had the highest. SNS and EWS had similar levels of LTP, which were in between the SWS and ENS groups. Corticosterone blood levels measured by an ELISA showed significant increases in the stressed groups compared to the non-stressed groups. The radial arm maze showed that both groups of exercise mice made fewer reference memory errors the second week of testing compared to the sedentary groups. RT-qPCR determined that brain-derived neurotrophic factor (BDNF) and corticoid and dopamine 5 receptors were likely causing some of the memory changes.

Made available in DSpace on 2014-12-17T15:37:03Z (GMT). No. of bitstreams: 1 DiegoSS_DISSERT.pdf: 636795 bytes, checksum: 620ad21d2b47550b5781855775d7f30a (MD5) Previous issue date: 2011-05-17 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Memory and anxiety are related phenomena. Several evidences suggest that anxiety is fundamental for learnining and may facilitate or impair the memory formation process depending of the context. The majority of animal studies of anxiety and fear use only males as experimental subjects, while studies with females are rare in the literature. However, the prevalence in phobic and anxiety disorders is greater in women than in men. Moreover, it is known that gender maybe influence benzodiazepine effects, the classic drugs used for anxiety disorders treatment. In this respect, to further investigate if fear/anxiety aspects related to learning in female subjects would contribute to the study of phobic and anxiety disorders and their relationship with learning/memory processes, the present work investigates (a) the effects of benzodiazepine diazepam on female rats performance in a aversive memory task that assess concomitantly anxiety/emotionality, as the interaction between both; (b) the influence of estrous cycle phases of female rats on diazepam effects at aversive memory and anxiety/emotionality, and the interaction between both and (c) the role of hormonal fluctuations during estrous cycle phases in absence of diazepam effects in proestrus, because female rats in this phase received or not mifepristone, the antagonist of progesterone receptor, previously to the diazepam treatment. For this purpose, the plus maze discriminative avoidance task, previously validated for studies of anxiety concomitantly to learning/memory, was used. The apparatus employed is an adaptation of a conventional plus maze, with two opens arms and two closed arms, one of which presenting aversive stimulation (noise and light). The parameters used were: time in non-aversive arm compared to time in aversive and percentage of time in aversive arm on several temporal divisions, in order to evaluate memory; percentage of time in open arms, risk assessment, head dipping and end exploring to evaluate anxiety ; and distance traveled for locomotion. In experiment I, we found anxiolytic effect of diazepam only for 4 mg/kg dose, however the amnestic effect appear at a dose of 2 mg/kg. In second experiment, rats were divided in groups according estrous cycle phase (metaestrus/diestrus, proestrus e estrus). In this experiment, when we considered estrous cycle phase or diazepam treatment, the results did not demonstrate any differences in anxiety/emotionality parameters. The amnestic effects of diazepam occur in female rats in metestrus/diestrus and estrus and is absent in proestrous rats. Proestrous female rats that received mifepristone exhibited the amnestic effect of diazepam and also anxiolytic effects, that it was not previously observed in this dose. The results have demonstrated dissociation of anxiolytic and amnestic diazepam effects, not previously observed in males; the absence of amnestic effect of diazepam in proestrous phase; and the possible role of progesterone in aversive memory over diazepam effect, because the mifepristone, associated with diazepam, caused amnestic effect in proestrus / A mem?ria e a ansiedade s?o fen?menos relacionados. Diversas evid?ncias sugerem que a ansiedade ? fundamental para o aprendizado, podendo facilitar ou prejudicar a forma??o de mem?rias dependendo da situa??o, o que se constitui num fator relevante tanto para o funcionamento normal dos processos cognitivos quanto para a compreens?o dos transtornos de ansiedade. A maioria dos estudos com modelos animais que se prop?e a estudar medo e ansiedade usa machos como sujeitos experimentais existindo, assim, escassez no estudo de f?meas na literatura. Entretanto, a preval?ncia para transtornos f?bico-ansiosos ? maior em mulheres do que em homens. Al?m disso, sabe-se que o g?nero pode influenciar o efeito de benzodiazep?nicos, f?rmacos classicamente utilizados no tratamento de transtornos de ansiedade. No intuito de contribuir para o estudo de transtornos f?bico-ansiosos e sua rela??o com processos de mem?ria e aprendizado, o presente trabalho investigou (a) os efeitos do benzodiazep?nico diazepam sobre o desempenho de ratas em uma tarefa de mem?ria aversiva com concomitante avalia??o da ansiedade/emocionalidade; (b) a influ?ncia das fases do ciclo estral de ratas no efeito do diazepam na ansiedade/emocionalidade e mem?ria aversiva, assim como a intera??o entre ambas e (c) o papel de flutua??es hormonais ao longo das fases do ciclo sobre aus?ncia do efeito do diazepam no proestro, pois ratas nessa fase receberam ou n?o o antagonista do receptor da progesterona, mifepristona, previamente ao tratamento com diazepam. Para isso, foi utilizado o modelo da esquiva discriminativa em labirinto cruz elevado, previamente validado para estudos envolvendo ansiedade e aprendizagem. O aparato utilizado ? uma adapta??o do labirinto em cruz elevado convencional, constitu?do de dois bra?os abertos e dois bra?os fechados sendo que um dos fechados tem uma estimula??o aversiva com som e luz. Foram utilizados os par?metros: tempo no bra?o n?o-aversivo comparado ao tempo no aversivo e percentual de tempo no bra?o aversivo em diferentes divis?es temporais para avaliar mem?ria; percentual de tempo nos bra?os abertos, avalia??o de risco, mergulhos de cabe?a e explora??o da ponta do bra?o aberto para ansiedade ; e dist?ncia percorrida para locomo??o. A partir da curva dose-resposta, no primeiro experimento, observamos o efeito ansiol?tico (4mg/kg) e amn?stico (2mg/kg) do diazepam. No segundo experimento, as ratas foram separadas de acordo com as fases do ciclo estral (metaestro/diestro, proestro e estro). N?o foram observadas diferen?as significativas na ansiedade/emocionalidade, nem entre fases do ciclo, nem do tratamento com diazepam (2mg/kg). O efeito amn?stico do diazepam ocorreu nas ratas em metaestro/diestro e estro, estando ausente nas ratas em proestro. Na presen?a da mifepristona as ratas em proestro exibiram o efeito amn?stico do diazepam e tamb?m passaram a apresentar efeito ansiol?tico, o qual n?o havia sido observado previamente nesta dose. Os resultados demonstraram dissocia??o de efeitos amn?sticos e ansiol?ticos em f?meas, n?o previamente observada em machos; aus?ncia do efeito amn?stico do diazepam no proestro, que ocorre nas outras fases e o poss?vel papel da progesterona na mem?ria aversiva sob efeito do diazepam, uma vez que a mifepristona possibilitou o efeito amn?stico no proestro, fase na qual os n?veis de progesterona est?o elevados