Synthesis of spirocyclic 1,2-diamines by dearomatising intramolecular diamination of phenols

The stereocontrolled synthesis of complex spirotricyclic systems containing an embedded syn-1,2-diaminocyclohexane unit is reported, based upon a dearomatising oxidation of phenols bearing pendant ureas capable of acting as double nucleophiles. This complexity-generating transformation yields products with rich functionality suitable for application in the synthesis of potentially bioactive compounds

Prevalence, symptoms and management of uterine fibroids: an international internet-based survey of 21,746 women

<p>Abstract</p> <p>Background</p> <p>In 2009 the Uterine Bleeding and Pain Women's Research Study (UBP-WRS) was conducted interviewing 21,479 women across 8 countries in order to gain patient-based prevalence data on uterine pain and bleeding indications and investigate uterine symptoms and women's treatment experiences. This article shows relevant results of the study for the indication uterine fibroids providing data on self-reported prevalence, symptomatology and management of uterine fibroids.</p> <p>Methods</p> <p>2,500 women (USA: 4,500 women) in each country (Brazil, Canada, France, Germany, Italy, South Korea, the UK, the USA) completed an online survey. Women included were in their reproductive age (age group 15-49 years; USA: 18-49 years) and had ever experienced menstrual bleedings. Quotas were applied for age, region, level of education and household income of respondents. Variables have been analyzed descriptively and exploratory statistical tests have been performed.</p> <p>Results</p> <p>The self-reported prevalence of uterine fibroids ranged from 4.5% (UK) to 9.8% (Italy), reaching 9.4% (UK) to 17.8% (Italy) in the age group of 40-49 years. Women with a diagnosis of uterine fibroids reported significantly more often about bleeding symptoms than women without a diagnosis: heavy bleedings (59.8% vs. 37.4%), prolonged bleedings (37.3% vs. 15.6%), bleeding between periods (33.3% vs. 13.5%), frequent periods (28.4% vs. 15.2%), irregular and predictable periods (36.3% vs. 23.9%). Furthermore women with diagnosed uterine fibroids reported significantly more often about the following pain symptoms: pressure on the bladder (32.6% vs. 15.0%), chronic pelvic pain (14.5% vs. 2.9%), painful sexual intercourse (23.5% vs. 9.1%) and pain occurring mid-cycle, after and during menstrual bleeding (31.3%, 16.7%, 59.7%, vs. 17.1%, 6.4%, 52.0%). 53.7% of women reported that their symptoms had a negative impact on their life in the last 12 month, influencing their sexual life (42.9%), performance at work (27.7%) and relationship & family (27.2%).</p> <p>Conclusions</p> <p>Uterine fibroid is a common concern in women at fertile age causing multiple bleeding and pain symptoms which can have a negative impact on different aspects in women's life.</p

Catechol-O-Methyltransferase Expression and 2-Methoxyestradiol Affect Microtubule Dynamics and Modify Steroid Receptor Signaling in Leiomyoma Cells

CONTEXT: Development of optimal medicinal treatments of uterine leiomyomas represents a significant challenge. 2-Methoxyestradiol (2ME) is an endogenous estrogen metabolite formed by sequential action of CYP450s and catechol-O-methyltransferase (COMT). Our previous study demonstrated that 2ME is a potent antiproliferative, proapoptotic, antiangiogenic, and collagen synthesis inhibitor in human leiomyomas cells (huLM). OBJECTIVES: Our objectives were to investigate whether COMT expression, by the virtue of 2ME formation, affects the growth of huLM, and to explore the cellular and molecular mechanisms whereby COMT expression or treatment with 2ME affect these cells. RESULTS: Our data demonstrated that E(2)-induced proliferation was less pronounced in cells over-expressing COMT or treated with 2ME (500 nM). This effect on cell proliferation was associated with microtubules stabilization and diminution of estrogen receptor alpha (ERalpha) and progesterone receptor (PR) transcriptional activities, due to shifts in their subcellular localization and sequestration in the cytoplasm. In addition, COMT over expression or treatment with 2ME reduced the expression of hypoxia-inducible factor -1alpha (HIF-1 alpha) and the basal level as well as TNF-alpha-induced aromatase (CYP19) expression. CONCLUSIONS: COMT over expression or treatment with 2ME stabilize microtubules, ameliorates E(2)-induced proliferation, inhibits ERalpha and PR signaling, and reduces HIF-1 alpha and CYP19 expression in human uterine leiomyoma cells. Thus, microtubules are a candidate target for treatment of uterine leiomyomas. In addition, the naturally occurring microtubule-targeting agent 2ME represents a potential new therapeutic for uterine leiomyomas

The burden, distribution and risk factors for cervical oncogenic human papilloma virus infection in HIV positive Nigerian women

Background: The expected reduction in cervical cancer incidence as a result of increased access to antiretroviral therapy is yet to be seen. In this study we investigated the effect of HIV infection and treatment on high-risk (hr) human papilloma virus (HPV) prevalence and distribution. Methods: Cervical cells from 515 (220 HIV positive and 295 HIV negative) women, recruited during community cervical cancer screening programme in states of Ogun and Lagos and at the cervical cancer screen clinic, Nigerian Institute of Medical Research Lagos were evaluated for the presence of 13 hr HPV genotypes by polymerase chain reaction based assay. Results: The prevalence of high-risk HPV was 19.6% in the studied population. HPV 16 (3.9%), 35 (3.5%), 58 (3.3%) and 31 (3.3%) were the most common hr HPV infections detected. We observed that the prevalence of hr HPV was higher in HIV positives (24.5%) than 15.9% in HIV negative women (OR = 1.7; 95% CI: 1.1-2.7). A multivariate logistic regression analysis showed a lower hr HPV prevalence in HIV positive women on antiretroviral drugs (OR = 0.4; 95% CI: 0.3-0.5) and with CD4 count of 500 and above (OR = 0.7; 95% CI: 0.5-0.8). A higher prevalence of hr HPV was also noted in HIV positive women with CD4 count <200 cells/mm3 (OR = 2.4; 95% CI: 1.7-5.9). Conclusion: HPV 16, 35, 58 and 31 genotypes were the most common hr HPV infection in our study group, which could be regarded as high risk general population sample; with higher prevalence of HPV 16 and 35 in HIV positive women than in HIV negative women. The use of antiretroviral drugs was found to be associated with a lower prevalence of hr HPV infection, compared to those not on treatment. This study raises important issues that should be further investigated to enable the development of robust cervical cancer prevention and control strategies for women in our setting

Knowledge of sickle cell disease among parturiant mothers in Benin City and their attitude to newborn screening.

BACKGROUND; Sickle cell disease is the commonest genetic disorder of the black race. A high prevalence of the disease has been established. The disease is associated with a high level of mortality. However, it is yet to be established the knowledge and attitude of the mothers’ in this community to SCD and to ascertain the attitude of mothers to the screening of their healthy newborns.AIMS AND OBJECTIVES: The aim of this study was to determine the maternal knowledge of SCD and its mode of inheritance, to assess the mothers’ knowledge of her phenotype status and that of her partner and to determine the willingness of the mothers to accept screening for theirhealthy infants.METHODS: All consecutively newly delivered mothers who attended St Philomena’s Hospital Benin City, Nigeria were recruited into this study. They were assessed using a pretested questionnaire a sample of which will be shown in the text.RESULTS: Six hundred and twenty two (622) mothers were interviewed. Of these, 608 (97.7%) had heard of children popularly referred to as “sicklers” while 14 (2.3%) had not heard of children with such disease. Of the 608 mothers who had heard of the disease, only 213 (35%) could adequately describe the common features of the disease, 334 (55%) mothers thought they were normal and healthy children, while the remaining 61 (10%) mothers said they had no idea what children with SCD looked like. Of the 608 mothers who had heard of the disease, 369 (60.7%) did not know how it was acquired, 97 (16%) thought the disease ran in some families, while 142 (23.3%) appreciated that the diseasewas inherited by the children when both parents are carriers of the abnormal gene. Four hundred and thirty five (69.9%) of the mothers studied did not know their haemoglobin phenotype status. Four hundred and three (92.6%) of these did not know that of their partner either. Of the one hundred and eighty seven (30.1%) mothers knew their phenotypes, 129(20.7%) were AA, 55 (8.8%) were AS, 1(0.2%) was AC, while 2 (0.4%) had SCD; 1 SS, 1 SC). In 76.8% of the mothers studied, the haemoglobin phenotype status of the fathers was equally not known.CONCLUSION: Despite the high prevalence of SCD in our community, mother are still largely unaware of the disease and its mode of inheritance. The implication of this is that for affected children, the need to check for the disease usually arises when they develop a crisis complication of the disease.Keywords: Mothers’ knowledge, Attitude, Sickle cell disease, Newborn screening