O misoprostol é um análogo da prostaglandina E1, que inicialmente foi comercializado para o tratamento de ulceras gástricas. Estudos prévios já identificaram este fármaco como um teratógeno responsável por morte fetal e anomalias congênitas no embrião exposto, como defeitos de redução de membros e Seqüência de Möbius, porém ainda não se conhece o risco exato desta exposição. Atualmente, a comercialização no Brasil está proibida e seu uso é restrito ao ambiente hospitalar em situações obstétricas, por promover a contratilidade uterina, sendo útil na indução do parto com feto vivo, interrupção da gravidez com o feto morto e retido, aborto terapêutico e, em alguns casos de aborto incompleto e hemorragia pós-parto. Mesmo com a venda restrita, é popularmente usado em tentativas de aborto, uma vez que esta prática não é legalizada no Brasil. O objetivo deste estudo foi o de verificar a incidência de defeitos congênitos maiores em uma amostra de bebês expostos intra-útero ao misoprostol. Foram avaliadas 147 gestantes, no período de 1990-2007, que fizeram contato com três SIATs no Brasil (Sistema Nacional de Informação sobre Agentes Teratogênicos - serviço gratuito que fornece informações atualizadas sobre os riscos relacionados a exposições a agentes potencialmente teratogênicos na gestação) pelo uso do misoprostol durante a gravidez. Comparando os bebês expostos e não expostos, houve diferença significativa quanto à ocorrência de aborto (28/147 nos casos e 8/147 nos controles, P=0,001), intercorrência neonatal (15/147 nos casos e 4/147 nos controles, P=0,016) e prematuridade (11/111 nos casos e 2/135, P=0,004). As malformações mostraram uma significância de P= 0,121, porém tiveram um aumento de seis vezes no grupo das gestantes expostas ao misoprostol (6/147) comparado ao grupo controle (1/147), o que sugere o potencial teratogênico do misoprostol na gestação. / Misoprostol is an E1 prostaglandin analogue, which was initially commercialized in Brazil for the treatment of gastric ulcers. Early studies have identified this drug as a teratogen responsible for fetal death and congenital anomalies, such as limb reduction and Moebius Sequence, in embryos exposed; however, the exact risk of exposure to misoprostol is still unknown. Presently, its commercialization is prohibited in Brazil, and it is restricted to obstetric use in hospital environments, for promotine uterine contraction, being useful in labor induction of live fetus, pregnancy interruption of dead and retained fetus, therapeutic abortion, and in some cases of incomplete abortion and post-labor hemorrhage. Even though its sale is restricted, since abortion is illegal in Brazil, it is popularly used in abortion attempts. The objective of this study was to verify the incidence of major congenital defects in a sample of babies exposed intra-uterus to misoprostol. Between 1990 and 2007, 147 pregnant women were evaluated; they contacted three SIATs (National Information System on Teratogens, a free Brazilian service that provides current information on the risks related to exposure to potentially teratogenic agents during pregnancy) due to the use of misoprostol during their pregnancy. Comparing exposed babies to non-exposed babies, there was a significant difference as to the occurrence of abortion (28/147 in cases and 8/147 in controls, P=0.001), neonatal complications (15/147 in cases and 4/147 in controls, P=0.016), and prematurity (11/111 in cases and 2/135 in controls, P=0.004). Malformations showed a significance of P=0.121 and an increase by sixfold in the group of pregnant women exposed to misoprostol (6/147) when compared to the control group (1/147), which suggests the teratogenic potential of misoprostol in pregnancy.

Objective Postpartum hemorrhage (PPH) is a major cause of maternal mortality world-wide; misoprostol is a relatively cheap, easily administered, and an efficient medication to be given after the delivery of the baby to prevent PPH, thus posing it as a first choice in resource-poor communities. The aim of this study is to answer questions regarding the most appropriate dose (400 µg versus 600 µg), effect of labour settings (community or clinical), and management of labour on misoprostol effectiveness and safety in preventing PPH. Methods We developed a search strategy and conducted a search within five key databases. Two reviewers screened the articles for predefined inclusion/exclusion criteria, quality, and performed data extraction. Discrepancy was dealt with by reaching consensus. In article 1, we only included randomized controlled trials, we performed a random-effects Bayesian network meta-analysis comparing 400 µg to 600 µg misoprostol over five outcomes of interest: blood loss ≥500 ml, blood loss ≥1000 ml, using additional uterotonics, shivering, and pyrexia. In article 2, we included any experimental trial, we performed a random effects model meta-analysis, pooling the incidence of PPH from each misoprostol arm. Subsequently, a meta-regression model was performed on identified potential effect-modifiers, including clinical settings and labour management. Results Of 444 identified records, 46 trials met the inclusion/exclusion criteria in article 1, and 56 trials in article 2. The odds ratio (OR) of misoprostol 400 µg vs. 600 µg for bleeding ≥ 500 ml is 0.86 [95% Credible Intervals: 0.46 − 1.54], for bleeding ≥ 1000 ml the OR is 0.83 [95% CrI 0.54 – 1.26], for additional uterotonics is 0.75 [95% CrI 0.40 – 1.40], for pyrexia and shivering an OR of 0.57 [95% CrI 0.15 – 2.18] and 0.63 [95% CrI 0.29 – 1.31] respectively. The overall incidence of PPH was 6.62 per 100 pregnancies (95%CI 4.71 per 100 – 8.53 per 100). Labour settings and other aspects of active management of labour had no statistically significant effect on the incidence of post-partum hemorrhage. Conclusion We found no difference between the administration of misoprostol 400 µg or 600 µg for the prevention of PPH and side effects of misoprostol, as well as no effect of labour settings and management of labour on misoprostol effectiveness.

Nonsteroidal anti-inflammatory drugs (NSAIDs), non-selective or selective inhibitors of cyclooxygenase (COX-1 and -2), reduce pain and inflammation associated with arthritic diseases. Celecoxib, a COX-2-selective inhibitor providing decreased gastric injury relative to non-selective NSAIDs, is commonly prescribed. Misoprostol, a prostaglandin analog, supplements NSAID-inhibited prostaglandin levels. As concomitant celecoxib and misoprostol administration has been shown to intensify renal adverse effects, this article examined the influence of concomitant administration on hepatic histopathology, oxidative stress, and celecoxib concentration. On days 1 and 2, rat groups (n = 6) were gavaged twice daily (two groups with vehicle and two groups with 100 μg/kg misoprostol). From day 3 to day 9, one celecoxib dose (40 mg/kg) replaced a vehicle dose of one group and one group received celecoxib in addition to misoprostol. Livers were harvested on day 10. No hepatic abnormalities were observed denoting a lack of influence by either drug. Also no change in mean biomarker levels was detected. The changes in hepatic celecoxib concentration in the misoprostol-receiving group compared to control were not significant. Thus misoprostol does not influence hepatic celecoxib effects in terms of histopathology, oxidative stress, or celecoxib concentration level at the dosage and duration examined.

Autoregulation of renal blood flow is partly mediated by antagonistic vasodilating and vasoconstricting effects of products of the arachidonic acid cascade. Vasodilatory prostaglandins have been evaluated in experimental models of acute renal failure and clinical human medicine, with variable results. This study assessed potential protective effects of an oral prostaglandin E₁ analogue, misoprostol, in gentamicin-induced nephrotoxicosis in dogs. Twelve dogs were initially assessed to be clinically healthy and to have normal renal function. Each received gentamicin (10 mg/kg intravenously, every 8 hours) for 8 days. Six dogs received oral placebo and 6 received misoprostol (3 µg/kg by mouth, every 8 hours) for the duration of study. Serum biochemical profiles, urinalyses, and exogenous creatinine clearances were monitored every 2 to 3 days. Three dogs receiving misoprostol were withdrawn early because of severity of clinical signs. Changes in serum urea nitrogen, creatinine, potassium, chloride, total protein, and urine protein-to-creatinine ratio appeared more severe in dogs receiving misoprostol, but were not significantly different between groups over time. Exogenous creatinine clearances were significantly decreased in dogs receiving misoprostol. Histopathological changes included patchy necrosis of renal proximal and were not significantly different between groups. Administration of misoprostol appeared to adversely affect glomerular filtration rates in this model of acute nephrotoxicosis in dogs. In previous studies, supplementing vasodilatory prostaglandins in experimental acute renal failure had beneficial effects or there were no changes in renal function. Additional study is needed to assess effects of manipulating vasoactive products of the arachidonic acid cascade in renal failure. / Master of Science

Background and Objectives: Postpartum haemorrhage (PPH) and mother to child transmission (MTCT) of the Human Immune Deficiency Virus (HIV) are major threats to maternal and foetal health, especially in low and middle income countries. This thesis addressed two main objectives: 1) to investigate strategies for the prevention of PPH, with a focus on misoprostol; 2) to investigate strategies for prevention of mother to child transmission (PMTCT) of HIV, with a focus on the male partner. Methods: We employed a number of study designs including a cross sectional design, a retrospective chart review, and a systematic review which included Classical and Bayesian approaches of meta- analysis. Key methodological issues addressed include the use of propensity score matching methods to address channeling bias; comparison and combination of evidence from different sources; sensitivity analysis in health research; and methods for developing new tools for measurement in health research. Results and Conclusions: Our findings suggests that an oxytocin-misoprostol combination is better than the current standard of care of oxytocin-only which is recommended by the World Health Organisation for the prevention of PPH. Secondly, effectiveness data from well-designed observational studies may be used to inform clinical decisions on misoprostol in the prevention of PPH. Thirdly, using a new tool we have created, it is possible to objectively identify HIV positive women who lack the support of their male partners in adhering to PMTCT recommendations. / Background and Objectives: Postpartum haemorrhage (PPH) and mother to child transmission (MTCT) of the Human Immune Deficiency Virus (HIV) are major threats to maternal and foetal health, especially in low and middle income countries. This thesis addressed two main objectives: 1) to investigate strategies for the prevention of PPH, with a focus on misoprostol; 2) to investigate strategies for prevention of mother to child transmission (PMTCT) of HIV, with a focus on the male partner. Methods: We employed a number of study designs including a cross sectional design, a retrospective chart review, and a systematic review which included Classical and Bayesian approaches of meta- analysis. Key methodological issues addressed include the use of propensity score matching methods to address channeling bias; comparison and combination of evidence from different sources; sensitivity analysis in health research; and methods for developing new tools for measurement in health research. Results and Conclusions: Our findings suggests that an oxytocin-misoprostol combination is better than the current standard of care of oxytocin-only which is recommended by the World Health Organisation for the prevention of PPH. Secondly, effectiveness data from well-designed observational studies may be used to inform clinical decisions on misoprostol in the prevention of PPH. Thirdly, using a new tool we have created, it is possible to objectively identify HIV positive women who lack the support of their male partners in adhering to PMTCT recommendations. / Thesis / Doctor of Philosophy (PhD)

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / avaliar a perda sanguÃnea em partos vaginais induzidos pelo misoprostol e em cesÃreas com tentativa prÃvia de induÃÃo do parto pelo misoprostol, atravÃs da dosagem de hemoglobina prà e pÃs-parto; avaliar a perda sanguÃnea em partos vaginais espontÃneos e cesÃreas eletivas, atravÃs da dosagem de hemoglobina prà e pÃs-parto; comparar a perda sanguÃnea, avaliada pela dosagem de hemoglobina prà e pÃs-parto, entre partos induzidos e partos nÃo induzidos. Sujeitos e mÃtodos: realizou-se estudo na Maternidade-Escola Assis Chateaubriand da Universidade Federal do CearÃ, em 101 gestantes com indicaÃÃo para induÃÃo do trabalho de parto, que foram avaliadas pela dosagem de hemoglobina prà e pÃs-parto para estimativa da perda sanguÃnea no parto. As pacientes foram submetidas à ultrassonografia obstÃtrica transabdominal para avaliaÃÃo da estÃtica e peso fetais e Ãndice de lÃquido amniÃtico, e à cardiotocografia basal para avaliaÃÃo da vitalidade fetal. Procedeu-se à induÃÃo do trabalho de parto com misoprostol 25mcg, via vaginal. Os comprimidos foram administrados a cada 6 horas, em um nÃmero mÃximo de seis. O grupo controle foi composto por 30 pacientes que entraram em trabalho de parto espontaneamente e por 30 pacientes que se submeteram à cesÃrea eletivamente. A anÃlise estatÃstica foi realizada com o programa SPSS 10.0 (SPSS Co, Chicago, IL, USA). Os dados foram descritos atravÃs de mÃdias, desvios-padrÃo, medianas, mÃnimos, mÃximos, freqÃÃncias absolutas (n) e relativas (%). Os testes utilizados foram os de comparaÃÃo de mÃdias: T de Student pareado; de medianas: Mann-Whitney, Qui-quadrado ou Exato de Fisher; e o Coeficiente de correlaÃÃo de Spearman. O estudo da hemoglobina, antes e depois do parto foi avaliado atravÃs de ANOVA para medidas repetidas, onde foram verificados o efeito do tempo (prà e pÃs-parto) e o efeito do grupo (com e sem uso do misoprostol). Resultados: foram observadas diferenÃas significativas no tempo, em ambos os tipos de partos (p<0.0001), mas nÃo entre os grupos (p > 0.05). Portanto, existem diferenÃas significativas entre os nÃveis hemoglobina prà e pÃs-parto (p < 0.0001), porÃm as diferenÃas sÃo proporcionais em ambos os grupos, ou seja, a diferenÃa ocorre tanto no grupo que fez uso do misoprostol quanto no grupo que nÃo fez uso do misoprostol (a diminuiÃÃo foi a mesma em ambos os grupos), tanto na cesÃrea (p=0.6845) quanto no parto normal (p=0.2694). ConclusÃes: a induÃÃo do parto com misoprostol nÃo altera a perda sanguÃnea durante o parto, tanto nos partos vaginais induzidos, quanto nas cesÃreas com tentativa prÃvia de induÃÃo, quando comparada respectivamente com a perda sanguÃnea em partos vaginais espontÃneos e cesÃreas eletivas. / ABSTRACT Objectives: to evaluate the blood loss in induced vaginal delivery by misoprostol and caesarians section with induction attempt, through the hemoglobin blood levels pre and post delivery. To evaluate the blood loss in spontaneous vaginal deliveries and elective caesarians through the hemoglobin blood levels pre and post delivery. To compare the blood loss, evaluated by the hemoglobin blood levels pre and post delivery between induced and non induced deliveries. Subjects and methods: this study included 101 pregnant women admitted to the Assis Chateaubriand Maternity School of the Federal University of Cearà which met the criteria for induced delivery labor. Patients were submitted to transabdominal obstetric ultrassound for evaluation of the static and fetal weight and amniotic liquid index, and basal cardiotocography in order to evaluate fetal vitality. Procedures were taken for induced labor delivery with misoprostol 25mcg, by vaginal rout. The pills were administered each 6 hours in a maximum number of six. The control group was formed by 30 patients that initiated labor spontaneously and 30 patients that achieved caesarians electively. The statistical analysis was done with the program SPSS10.0 (SPSS Co, Chicago, IL, USA). The data were described through the medium, standard deviation, median, minimum, maximum, absolute (n) and relative (%) frequencies. The tests used for comparison of media: T of student; of median: Mann-Whitney, Qui-square or Exact of Fisher; and the Coefficient of Spearman correlation. The evaluation of hemoglobin levels before and after delivery was analyzed through the ANOVA test for repeated values, taking in account the effect of time (pre and post delivery) and the effect of the group (with and without the use of misoprostol). Results: there was a statistically significant difference between time in both types of delivery (p<0.0001).There were no statistical significance between the groups (p>0.05). Additionally, there was a similar pattern of decrease in hemoglobin blood levels pre and post labor in both groups evaluated, in the caesarian delivery (p=0.6845) and normal delivery as well (p=0.2694). Conclusions: labor induction with misoprostol does not modify the blood loss during induced vaginal deliveries and caesarians section with induction attempt, when compared to, respectively, the blood loss in spontaneous vaginal deliveries and in elective caesarians.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Objetivos: comparar a mensuraÃÃo ultra-sonogrÃfica transvaginal do colo uterino e o Ãndice de Bishop, na prediÃÃo do parto vaginal apÃs induÃÃo do trabalho de parto com misoprostol 25mcg, assim como, determinar os principais fatores relacionados à evoluÃÃo para parto vaginal. Sujeitos e MÃtodos: realizou-se estudo de validaÃÃo de tÃcnica diagnÃstica na Maternidade-Escola Assis Chateaubriand da Universidade Federal do CearÃ, com 126 gestantes com indicaÃÃo para induÃÃo do trabalho de parto que foram avaliadas pelo Ãndice de Bishop e ultra-sonografia transvaginal para mensuraÃÃo cervical. As pacientes foram submetidas à ultra-sonografia obstÃtrica transabdominal, para avaliaÃÃo da estÃtica e peso fetais e Ãndice de lÃquido amniÃtico, e à cardiotocografia basal para avaliaÃÃo da vitalidade fetal. Procedeu-se à induÃÃo do trabalho de parto com misoprostol vaginal e sublingual, um dos comprimidos contendo 25mcg da droga e o outro apenas placebo. Os comprimidos foram administrados a cada seis horas, em um numero mÃximo de oito. A anÃlise estatÃstica foi realizada com o programa SPSS 10.0 (SPSS Co, Chicago, IL, USA), utilizando-se distribuiÃÃo de frequÃncias, mÃdias, desvios-padrÃo e medianas; assim como, anÃlise univariada e construÃÃo de curvas ROC, correlacionando Ãndice de Bishop e parto vaginal, e medida ultra-sonogrÃfica do colo uterino e parto vaginal. Em anÃlise multivariada foram pesquisadas outras variÃveis relacionadas ao parto vaginal. Resultados: atravÃs de curva ROC correlacionando a mensuraÃÃo do colo uterino por ultra-sonografia transvaginal e a evoluÃÃo para o parto vaginal, evidenciou-se uma Ãrea sob a curva de 0,513 com p=0,801. Outra curva ROC, analisando a relaÃÃo da avaliaÃÃo cervical pelo Ãndice de Bishop com o parto vaginal, demonstrou Ãrea sob a curva de 0,617 com p=0,025. AtravÃs de anÃlise de regressÃo logÃstica mÃltipla, evidenciou-se paridade &#8805; 1, escore de Bishop &#8805; 4 e presenÃa de lÃquido amniÃtico claro como associados à evoluÃÃo para o parto vaginal. ConclusÃes: a medida ultra-sonogrÃfica transvaginal do colo uterino nÃo foi boa preditora da evoluÃÃo para parto vaginal em pacientes com trabalho de parto induzido com misoprostol. O Ãndice de Bishop foi melhor preditor para parto vaginal nestas circunstÃncias. Os fatores preditivos mais importantes para parto vaginal, apÃs induÃÃo com misoprostol, foram paridade &#8805; 1, Ãndice de Bishop &#8805; 4 e presenÃa de lÃquido amniÃtico claro

The mechanisms involved in human parturition, and the molecular changes that occur during the transition from pregnancy and birth are not completely elucidated. Endogenous or administered prostaglandins, including the PGE1 and PGE2, are related to contractile activity and cervical ripening, playing an important role on labor. Due to maternal or fetal causes, some pregnancies require labor induction. In many cases, prostaglandins, including Dinoprostone (PGE2) and Misoprostol (PGE1 analog), are used for labor induction. However, the response to labor induction is variable, and the reasons why this occurs are unknown. Once delivery also involves modulation of oxidative metabolism, that can be potentially affected by administered drugs, in the present study, we analyzed prostaglandin E2 receptor (EP1, EP2, EP3 and EP4) gene expression of myometrial and cervical cells, in vivo and in vitro, as well as oxidative markers in myometrial cells exposed in vitro to different concentrations of Misoprostol. In both studies, tissue biopsies were obtained from pregnant women at term. In the in vivo study, from women with spontaneous deliveries or Dinoprostone induced labors, responsive or non-responsive to labor induction, and in the in vitro study, from women with spontaneous and non-spontaneous labors, these induced with misoprostol. Gene expression was analyzed by qtRT-PCR and oxidative biomarkers by spectrophotometric and fluorimetric analysis. The results obtained from the in vivo study showed a concurrent and antagonic regulation of EP1 and EP3 mRNA expression in cervical and myometrial tissues in pregnant women at term in Dinoprostone induced labors. EP1 mRNA was upregulated in the cervical tissue of women who did not respond to Dinoprostone induction. In addition, in the myometrium, significantly higher levels of EP3 mRNA were observed in women treated with Dinoprostone, independent of their responsiveness, indicating a possible regulation of the EP3 gene at a transcriptional level. In vitro analysis revealed that myometrial cells derived from women with spontaneous labors showed greater capacity for misoprostol genomic response, since an overexpression of genes associated with muscle contraction (EP1 and EP3) was observed. In addition, Misoprostol was able to differentially modulate two important oxidative metabolism markers (protein carbonylation and lipid peroxidation). However, this effect was dependent on cells source (whether obtained from spontaneous or non-spontaneous labors) and drug concentration. The results suggest that, in term pregnant women, there is modulation of the PGE2 receptors genes in myometrial and cervical tissues in Dinoprostone or Misoprostol-induced labors, and that the EPs have an important role in the success of spontaneous delivery and in the pharmacological response to PGE1 analog administration. Addicionally, oxidative metabolism also seems to play an important role in the parturition process, requiring further studies to define its real function in this process. / Os mecanismos pelo qual a parturição humana é iniciada espontaneamente e as mudanças moleculares que ocorrem durante a transição entre a gestação e o parto não são completamente elucidados. Um dos principais fatores envolvidos são as prostaglandinas, endógenas ou administradas, entre elas a PGE1 e PGE2, que estão relacionadas à atividade contrátil e ao amadurecimento cervical. Em casos de necessidade de antecipação do nascimento, as prostaglandinas, entre elas a Dinoprostona (PGE2) e o Misoprostol (análogo da PGE1), são utilizadas para indução do parto. Entretanto, a resposta à indução do parto é variável e os motivos pelos quais isto ocorre é desconhecido. Uma vez que o parto também envolve modulação do metabolismo oxidativo, que pode ser potencialmente afetado por ação de fármacos, no presente estudo analisamos a expressão dos genes dos receptores de prostaglandina E2 (EP1, EP2, EP3 e EP4) em células miometriais e cervicais, in vivo e in vitro, bem como marcadores oxidativos em células miometriais expostas in vitro a diferentes concentrações de Misoprostol. Para a realização dos dois estudos, foram obtidas biópsias teciduais em parturientes a termo; no estudo in vivo, em mulheres com parto espontâneo, responsivas e não responsivas à indução do parto com Dinoprostona e no estudo in vitro, em mulheres com partos espontâneos e não espontâneos, estes induzidos com Misoprostol. A expressão gênica foi analisada através de qtRT-PCR e no estudo in vitro, além das análises da modulação gênica, foram conduzidas análises complementares de biomarcadores oxidativos, através de ensaios espectrofotométricos e fluorimétricos. Nos resultados obtidos a partir do estudo in vivo, observou-se regulação concomitante e antagônica da expressão do mRNA de EP1 e EP3 nos tecidos cervical e miometrial em gestantes a termo com partos induzidos com Dinoprostona. O mRNA do EP1 foi superexpresso no tecido cervical de mulheres que não responderam à indução com Dinoprostona. Além disso, no miométrio, níveis significativamente mais elevados de mRNA do EP3 foram observados em mulheres tratadas com Dinoprostona, independente da sua capacidade de resposta, indicando uma possível regulação da expressão do gene EP3 a nível transcricional. A análise in vitro evidenciou que as células miometriais oriundas de mulheres com parto espontâneo apresentaram maior capacidade de resposta genômica ao Misoprostol, uma vez que uma superexpressão dos genes relacionados com a contração muscular (EP1 e EP3) foi observada. Adicionalmente, o Misoprostol foi capaz de modular diferencialmente dois importantes marcadores do metabolismo oxidativo (lipoperoxidação e carbonilação de proteínas). Porém, este efeito foi dependente da origem das células (se obtida de partos espontâneos ou não espontâneos) e da concentração do fármaco. Os resultados obtidos sugerem que, em gestantes a termo, existe modulação dos genes dos receptores de PGE2 no miométrio e colo em partos induzidos com Dinopostona ou Misoprostrol, e que os EPs possuem um papel relevante no sucesso do parto espontâneo e na resposta farmacológica aos análogos a prostaglandina E1. Adicionalmente, o metabolismo oxidativo também parece desempenhar um papel importante no processo da parturição, necessitando de estudos complementares para esclarecimento da sua real função neste processo.

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.

Tse On Ki. / Thesis submitted in: June, 1997. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (leaves 97-113). / Abstract also in Chinese. / List of Tables --- p.xiii / List of Figures --- p.xiv / List of Abbreviations --- p.xv / Chapter Chapter 1. --- Introduction to thesis --- p.2 / Chapter 1.1 --- Misoprostol --- p.2 / Chapter 1.1.1 --- Description and History of Drug --- p.2 / Chapter 1.1.2 --- Current Use in Obstetrics and Gynaecology --- p.3 / Chapter 1.1.2.1 --- Termination of Pregnancy (TOP) --- p.3 / Chapter 1.1.2.2 --- Cervix Priming prior to Surgical Treatment of Pregnancy Failure --- p.4 / Chapter 1.1.2.3 --- Medical management of spontaneous abortion --- p.4 / Chapter 1.2 --- Gemeprost --- p.4 / Chapter 1.3 --- Doppler Sonography and Assessment of Blood Velocity --- p.5 / Chapter 1.4 --- Overview of Thesis --- p.5 / Chapter 1.5 --- Aim of this Study --- p.8 / Chapter Chapter 2. --- Physiological and Anatomical Features of Pregnancy --- p.10 / Chapter 2.1 --- Cardiovascular System Changes in Pregnancy --- p.10 / Chapter 2.1.1 --- Changes in the Blood --- p.10 / Chapter 2.1.2 --- Changes in Circulation --- p.11 / Chapter 2.1.3 --- The Distribution of Blood Flow in Uterus --- p.12 / Chapter 2.2 --- Blood Supply to Uterus --- p.13 / Chapter 2.3 --- Pelvic Anatomy in Early Pregnancy via Transvaginal Sonography --- p.15 / Chapter 2.3.1 --- Uterus --- p.15 / Chapter 2.3.2 --- The Adnexa --- p.17 / Chapter 2.3.3 --- Other Pelvic Structures --- p.17 / Chapter Chapter 3. --- Prostaglandins and Analogues --- p.19 / Chapter 3.1 --- Natural Prostaglandins --- p.19 / Chapter 3.2 --- The Source of PGs in Reproductive Organs of Women --- p.19 / Chapter 3.3 --- PGs Synthesis and Metabolism --- p.20 / Chapter 3.4 --- PGE1 Analogue: Misoprostol --- p.21 / Chapter 3.4.1 --- Misoprostol --- p.22 / Chapter 3.4.1.1 --- Pharmacology --- p.22 / Chapter 3.4.1.2 --- Adverse Side Effects --- p.23 / Chapter 3.4.1.3 --- Toxicology --- p.23 / Chapter 3.4.1.4 --- Misoprostol in Obstetrics & Gynaecology --- p.24 / Chapter 3.4.1.4.1 --- To Induce Abortion in First and Second Trimesters --- p.24 / Chapter 3.4.1.4.2 --- Cervix Priming prior to Surgical Evacuation of Uterus --- p.27 / Chapter 3.4.1.4.3 --- Medical Management of Miscarriage --- p.28 / Chapter 3.4.1.4.4 --- Induction of Labour with Dead Fetus --- p.29 / Chapter 3.4.1.4.5 --- Induction of labour --- p.29 / Chapter 3.4.2 --- The Potential Dangers of PGE1 analogues --- p.30 / Chapter Chapter 4. --- Doppler Sonography and Parameter Measurements --- p.34 / Chapter 4.1 --- The Principles of Ultrasound and Doppler Sonography --- p.34 / Chapter 4.1.1 --- The Basic Principles of Ultrasound --- p.34 / Chapter 4.1.2 --- Principles of Doppler Sonography --- p.36 / Chapter 4.2 --- Doppler Mode --- p.39 / Chapter 4.2.1 --- Continuous Wave Doppler Imaging --- p.39 / Chapter 4.2.2 --- Pulsed Wave Doppler Systems --- p.39 / Chapter 4.2.3 --- Colour Doppler Sonography (CDS) --- p.40 / Chapter 4.3 --- The Instrument of Doppler Sonography --- p.40 / Chapter 4.4 --- "Resistance Indices - S/D, PI and RI" --- p.42 / Chapter 4.5 --- Flow Measurement of Uterine artery --- p.44 / Chapter 4.5.1 --- Sampling Sites and Waveforms --- p.44 / Chapter 4.5.2 --- Waveform Components --- p.45 / Chapter 4.5.3 --- Identification of the Main Uterine Arteries --- p.45 / Chapter 4.5.4 --- UA Waveform Changes in Normal Pregnancy --- p.46 / Chapter 4.5.5 --- Factors Affecting the UA Waveforms --- p.48 / Chapter 4.5.6 --- Uterine Artery Resistance in Normal Pregnancy and Labour --- p.49 / Chapter 4.5.6.1 --- Uterine Artery Resistance in Normal Pregnancy --- p.49 / Chapter 4.5.6.2 --- Uterine Artery Resistance during normal labour --- p.51 / Chapter 4.5.7 --- Doppler Measure of Fetal Heart Rate --- p.52 / Chapter 4.6 --- Sonography in Estimation of Gestational Age --- p.53 / Chapter Chapter 5. --- Research Protocol --- p.56 / Chapter 5.1 --- The Ethics --- p.56 / Chapter 5.2 --- Apparatus --- p.58 / Chapter 5.3 --- Drug and Dosage --- p.59 / Chapter 5.4 --- Research Protocol --- p.59 / Chapter 5.4.1 --- Subjects --- p.59 / Chapter 5.4.2 --- Transvaginal Scan --- p.60 / Chapter 5.4.3 --- Parameters Measured --- p.61 / Chapter 5.4.4 --- Misoprostol --- p.65 / Chapter 5.5 --- Data analysis --- p.66 / Chapter Chapter 6. --- Results --- p.68 / Chapter 6.1 --- The Patients' Characteristics --- p.68 / Chapter 6.2 --- The Intra-observer Error --- p.70 / Chapter 6.3 --- Results of Study --- p.70 / Chapter 6.3.1 --- Effect of Misoprostol on the S/D ratio of Both Uterine Arteries --- p.70 / Chapter 6.3.2 --- Effect of Misoprostol on the PI of Both Uterine Arteries --- p.73 / Chapter 6.3.3 --- Effect of Misoprostol on Fetal Heart Rate (FHR) --- p.76 / Chapter 6.3.4 --- Left and Right UA-S/D --- p.78 / Chapter 6.3.5 --- Left and Right UA-PI --- p.81 / Chapter 6.3.6 --- The relationship Between Subgroups --- p.84 / Chapter 6.3.7 --- Side Effects of Misoprostol --- p.85 / Chapter 6.3.8 --- The Changes of UA-S/D and UA-PI According to Gestation --- p.86 / Chapter Chapter 7. --- Discussions and Conclusions --- p.89 / Chapter 7.1 --- Difficulties Encountered during Study --- p.89 / Chapter 7.2 --- Results of Study --- p.90 / Chapter 7.3 --- Implications --- p.94 / Chapter 7.4 --- Summary of Thesis --- p.95 / Chapter 7.5 --- Conclusions --- p.96 / Chapter 8. --- References and Appendix --- p.97