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  • Löfgren, Magnus, 1979-, et al. (författare)
  • Withdrawal effects from progesterone and estradiol relate to individual risk-taking and explorative behavior in female rats
  • 2009
  • Ingår i: Stress- och könshormoners verkningar på centrala nervsystemet. - : Elsevier. ; 96:1, s. 91-97
  • Tidskriftsartikel (refereegranskat)abstract
    • Withdrawal from progesterone and estradiol has been used as an animal model of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). In the clinical population individual sensitivity to sex steroid hormones, personality and heredity influence PMS/PMDD. Understanding the phenotypic risk factors of PMS/PMDD and drug development requires an animal model which incorporates individual steroid sensitivity. The main objective of this study was to investigate whether the individual trait of risk-taking and exploration influence the severity of PEWD in female rats. Thirty-two female Wistar rats in their diestrus phase were tested in the open field (OF) and divided into high responders (HR) and low responders (LR). Injections were given i.p. twice daily for 6 days, either 5 mg/kg progesterone combined with 10 microg/kg 17beta-estradiol, or vehicle (sesame oil). After a 24-hour withdrawal the animals were tested in the elevated plus maze (EPM). Blood samples for CORT analysis were collected after both behavioral tests. The HR rats withdrawn from progesterone and estradiol, spent less time on the EPM open arms and had lower CORT levels than the HR controls. The LR group showed no differences in EPM behavior and CORT levels during PEWD. The controls showed a stable trait of risk-taking and exploration, indicated by behavioral and CORT level correlations between the OF and EPM tests. These findings show that female rats with the trait of risk-taking and explorative behavior (HR) are more affected by PEWD.
  • Löfgren, Magnus, 1979- (författare)
  • Behavioral effects of female sex steroid hormones : models of PMS and PMDD in Wistar rats
  • 2009
  • Ingår i: Stress- och könshormoners verkningar på centrala nervsystemet. - Umaå : Department of Clinical Sciences, Division of Obstetrics and Gynecology.
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Background Animal models can be used to mimic human conditions of psychopathology, and also as pre-clinical models to evaluate candidate drugs. With hormonal treatment it is possible to produce behavior in the rat which corresponds to the mental symptoms of pre-menstrual syndrome (PMS), and pre-menstrual dysphoric disorder (PMDD). PMS affects 25-30 % of all women in fertile age and 3-8% are diagnosed with the more severe condition PMDD. The cardinal mental symptoms are; irritability, mood-swings, depression, anxiety, fatigue, insomnia, difficulties with concentration and memory and learning difficulties. The symptoms of PMS/PMDD occur in the luteal phase in conjunction with increasing concentrations of progesterone (P4) and P4-metabolites. In anovulatory cycles the symptoms are absent. The hormones which produce the monthly reoccurring negative symptoms on mood are foremost the neuroactive metabolites; allopregnanolone (ALLO) and tetrahydro-deoxycorticosterone (THDOC). ALLO is produced by the corpus luteum, but can also be synthesized in the brain, both ALLO and THDOC can also be released from the adrenal cortex during stress. These steroids are active on the inhibitory GABA neurotransmitter system through the GABAA receptor, and the effects are similar to that of alcohol and benzodiazepines. These steroids have strong sedative and hypnotic effects. A paradox is that some individuals seem to react with negative mood on sex steroids while all fertile women have the cyclical steroid changes during the menstrual cycle. Some individuals are more sensitive to neuroactive steroids with influences of personality, heritability and stress factors. Aims The thesis aims were to develop pre-clinical animal models of PMS/PMDD and to investigate induction of ALLO tolerance, individual sensitivity to neurosteroids and the interactions between chronic social stress and neurosteroids. Methods In these studies male and female Wistar rats were used to test steroid hormone effects on learning and memory and behaviors analogous to negative mood symptoms. This was accomplished through hormonal treatment and a subsequent withdrawal period from P4 (P4) + estradiol (E2) (PEWD), or ALLO. To assess tolerance, memory and learning in the Morris water maze (MWM) was studied. Anxiety-like behaviors were tested with the elevated plus maze (EPM), open field test (OFT), and the intruder test (IT). The EPM or OFT was used to classify the rats as high or low responders on risk-taking and explorative behavior (HR/LR). For social ranking order assessment the tube test (TT) and food competition test (FCT) were used. Chronic social stress was accomplished through co-habituation with two older rats (chronic subordination stress). In female rats the estrous cycle followed using staining of vaginal smears. Concentration of corticosterone (CORT) was measured by radio-immuno-assay (RIA). Results In the MWM ALLO pre-treatment produced tolerance to the acute negative ALLO effects. Both male and female rats showed behavioral correlations between the EPM and OFT tests, and correlations were also seen in CORT levels. Individuals with the stable trait of high risk-taking and explorative behavior (HR) were more sensitive to PEWD induction of anxiety-like behavior. These animals also showed decreased CORT levels during withdrawal. Chronic subordination stress enhanced the response to PEWD on measures of locomotor activity and social anxiety-like behavior. Conclusions It is possible to induce tolerance to the negative ALLO effects on learning and memory. The animal models of anxiety-like behavior show an individual PEWD response profile where HR rats are more sensitive. Exposure to chronic social stress enhanced the PEWD response. Hence there are both inherent and environmental factors behind the behavioral response to steroid hormones in rats.
  • Idahl, Annika, 1965-, et al. (författare)
  • Chlamydia trachomatis, Mycoplasma genitalium, Neisseria gonorrhoeae, human papillomavirus, and polyomavirus are not detectable in human tissue with epithelial ovarian cancer, borderline tumor, or benign conditions
  • 2010
  • Ingår i: American Journal of Obstetrics and Gynecology. - 0002-9378 .- 1097-6868. ; 202:1, s. 71.e1-71.e6
  • Tidskriftsartikel (övrigt vetenskapligt)abstract
    • OBJECTIVE: We sought to analyze the presence of the microorganisms Chlamydia trachomatis, Mycoplasma genitalium, Neisseria gonorrhoeae, human papillomavirus (HPV), and the polyomaviruses BK virus (BKV) and JC virus (JCV) in ovarian tissues of women with ovarian carcinomas, borderline tumors, and benign conditions. STUDY DESIGN: Ovarian tissue, snap-frozen and stored at -80 degrees C, from 186 women with benign conditions, borderline tumors, and epithelial ovarian cancer, as well as tissue from the contralateral ovary of 126 of these women, were analyzed regarding presence of C trachomatis and N gonorrhoeae (transcription mediated amplification), M genitalium (real-time polymerase chain reaction [PCR]), HPV (PCR), and BKV and JCV (PCR). RESULTS: All the tissue samples studied were found negative for the microorganisms analyzed. CONCLUSION: C trachomatis, M genitalium, N gonorrhoeae, HPV, and the polyomaviruses BKV and JCV are not detectable in ovarian tissues either from women with benign conditions and borderline tumors or from women with ovarian cancer.
  • Brennan, Donal J., et al. (författare)
  • Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer
  • 2010
  • Ingår i: ; 10, s. 125-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. Methods: HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS). Results: Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade. Conclusion: HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens.
  • Nilsson, Ulrika (författare)
  • Det heta könet : Gynekologin i Sverige kring förra sekelskiftet
  • 2005
  • Bok (populärvet., debatt m.m.)abstract
    • När gynekologin etablerades på 1860-talet uppfattades kvinnan som radikalt annorlunda än mannen. Hon var den som avvek från normen och ansågs därför behöva en egen medicinsk specialitet. Hon blev patienten och Objektet, mannen läkaren och Subjektet. Idéhistorikern Ulrika Nilsson visar i sin bok Det heta könet hur gynekologin i Sverige växte fram runt förra sekelskiftet. Med belysande exempel från både kulturområdet och vetenskap visar hon hur gynekologin har fortsatt att upprätthålla och förstärka ett biologiskt skillnadstänkande i vårt samhälle.
  • Linge, Helena, et al. (författare)
  • The Antibacterial Chemokine MIG/CXCL9 Is Constitutively Expressed in Epithelial Cells of the Male Urogenital Tract and Is Present in Seminal Plasma.
  • 2008
  • Ingår i: Journal of Interferon and Cytokine Research. - : Mary Ann Liebert, Inc.. - 1079-9907. ; 28:3, s. 190-196
  • Tidskriftsartikel (refereegranskat)abstract
    • ABSTRACT The integrity of the urogenital tract against potentially invasive pathogens is important for the health of the individual, fertilization, and continuance of species. Antibiotic peptides with broad antimicrobial activity, among them chemokines, are part of the innate immune system. We investigated the presence of the antibacterial interferon (IFN)-dependent CXC chemokines, MIG/CXCL9, IP-10/CXCL10, and I-TAC/CXCL11, in the human male reproductive system. MIG/CXCL9 was detected at 25.0 nM (range 8.1-40.6 nM; n = 14), whereas IP-10/CXCL10 and I-TAC/CXCL11 were detected at lower levels (mean 1.8 nM, range 0.3-5.8 nM and mean 0.6, 0.2-1.6 nM, respectively) in seminal plasma of fertile donors. The levels of MIG/CXCL9 are more than 300-fold higher than those previously reported in blood plasma. In vasectomized donors, significantly lower levels of MIG/CXCL9 (mean 14.7 nM, range 6.6-21.8) were found, suggesting that the testis and epididymis, in addition to the prostate, significantly contribute to the MIG/CXCL9 content of seminal plasma. Strong expression of MIG/CXCL9 was found in the epithelium of testis, epididymis, and prostate, as detected by immunohistochemistry. MIG/CXCL9 at concentrations in the order of those found in seminal plasma possessed antibacterial activity against the urogenital pathogen Neisseria gonorrhoeae. The relatively high levels of MIG/CXCL9 in seminal plasma point to roles for this chemokine in both host defense of the male urogenital tract and during fertilization.
  • Wätterbjörk, Inger, 1955-, et al. (författare)
  • Reasons for declining extended information visit on prenatal screening among pregnant women and their partners
  • 2015
  • Ingår i: Prenatal Diagnosis. - : Wiley-Blackwell. - 0197-3851 .- 1097-0223. ; 35:12, s. 1232-1237
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: A two-step model on information on prenatal screening consists of brief information at the first visit at the Maternal Health Care Centre and an offer of extended information at a separate visit. There is a lack of knowledge why some pregnant women and their partners refrain from the extended information visit. The aim of this study was to explore their reasonsMethod: Eight qualitative interviews were analysed using Interpretive Description.Results: In the first theme “From an individual view”, the interviewees saw the invitation from their own points of view. They refrained because they did not want to receive any more information or had taken an individual position against chromosomal testing. In the theme, “From a societal view”, the interviewees perceived the offer as part of a societal view on prenatal screening that they could not support.Conclusion: The findings shows that these interviewees' reasons of declining an extended information visit are multidimensional and influenced by different views, from both an individual perspective and a more societal one. Health care professionals should be aware that some persons could have a different view on health care services and could be reluctant to accept offered services.
  • Bornehag, Carl-Gustaf, et al. (författare)
  • The SELMA study : a birth cohort study in Sweden following more than 2000 mother-child pairs
  • 2012
  • Ingår i: Paediatric and Perinatal Epidemiology. - Hoboken, USA : Wiley-Blackwell. - 0269-5022 .- 1365-3016. ; 26:5, s. 456-467
  • Tidskriftsartikel (refereegranskat)abstract
    • Background:  This paper describes the background, aim and study design for the Swedish SELMA study that aimed to investigate the importance of early life exposure during pregnancy and infancy to environmental factors with a major focus on endocrine disrupting chemicals for multiple chronic diseases/disorders in offspring.Methods: The cohort was established by recruiting women in the 10th week of pregnancy. Blood and urine from the pregnant women and the child and air and dust from home environment from pregnancy and infancy period have been collected. Questionnaires were used to collect information on life styles, socio-economic status, living conditions, diet and medical history.Results: Of the 8394 reported pregnant women, 6658 were invited to participate in the study. Among the invited women, 2582 (39%) agreed to participate. Of the 4076 (61%) non-participants, 2091 women were invited to a non-respondent questionnaire in order to examine possible selection bias. We found a self-selection bias in the established cohort when compared with the non-participant group, e.g. participating families did smoke less (14% vs. 19%), had more frequent asthma and allergy symptoms in the family (58% vs. 38%), as well as higher education among the mothers (51% vs. 36%) and more often lived in single-family houses (67% vs. 60%).Conclusions: These findings indicate that the participating families do not fully represent the study population and thus, the exposure in this population. However, there is no obvious reason that this selection bias will have an impact on identification of environmental risk factors.
  • Franzén, Karin, 1958-, et al. (författare)
  • Urinary incontinence : evaluation of an information campaign directed towards the general public
  • 2008
  • Ingår i: Scandinavian Journal of Urology and Nephrology. - 0036-5599 .- 1651-2065. ; 42:6, s. 534-538
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To study and evaluate the effect of an information campaign in the form of a brochure on urinary incontinence (UI) directed towards the general public, concerning knowledge, individual health behaviour, self-reported healthcare utilization and how the information was perceived.Material and methods. Within a community in central Sweden a random sample of the population, in age groups from 18 years upwards, was selected from the population registry, resulting in a total sample of 3658 people. The study group was sent the brochure "Treatment of urinary incontinence", produced by SBU (Swedish Council on Technology Assessment in Health Care) in March 2003 and a questionnaire 1–2 months after the brochure was received.Results. The overall response rate was 47.5%. Eighty per cent of the responders stated UI as an important health problem in society and 66% that they had gained new knowledge on UI. Twenty-eight per cent of the responders reported a current or previous history of UI, of whom 49% felt that they had received useful information for self-treatment and 21% had begun self-treatment.Conclusion. This population-based study found that the distribution of a brochure on UI to the general public was well received and can be an efficient method to spread knowledge and encourage self-management. 
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