Scutellaria barbata D. Don induces c-fos gene expression in human uterine leiomyomal cells by activating β2-adrenergic receptors

Scutellaria barbata D. Don (Lamiaceae; SB) inhibited the growth of uterine leiomyomal (LM) cells with unknown actions. The expression patterns of beta-adrenergic receptors (beta-ARs) in human uterine LM cells and functional coupling to gene expression have also been investigated. Northern blot analysis showed that beta-AR subtypes are expressed at different levels in the uterine LM cells and myometrial smooth muscle cells (SMCs). beta1-AR expression was to be found approximately at the same level in the two cell types. beta2-ARs were expressed at higher levels in uterine LM cells than that in myometrial SMCs. beta3-AR expression was not found in both the cells. c-fos gene expression was induced by SB in uterine LM cells via increases in adenosine-3',5', cyclic monophosphate (cAMP), which in turn activated the cAMP/protein kinase A (PKA) pathway. The PKA inhibitor, H89, inhibited c-fos gene expression induced by SB. It seems that the mechanism of proto-oncogenes c-fos different leiomyoma from other myometrial cancer. Further studies are necessary to elucidate whether c-fos induction by SB in uterine LM cells influences a regression of leiomyoma or induces other differentiation.     

Comparison of pulse methotrexate and pulse dactinomycin in the treatment of low-risk gestational trophoblastic neoplasia

Methotrexate and dactinomycin are efficient drugs in the treatment of patients with low-risk gestational trophoblastic neoplasia (LRGTN). To compare the effectiveness of these two drugs in LRGTN, 46 patients were randomised to receive weekly intramuscular methotrexate at 30 mg/m(2) (n = 28) or intravenous dactinomycin at 1.25 mg/m(2) every 2 weeks (n = 18). Fourteen patients (50%) in the methotrexate group and 16 patients (89%) in the dactinomycin group achieved complete response. Greater patient convenience and a lower number of required visits make dactinomycin superior to other alternatives.     

Sensitivity and specificity of mean corpuscular volume testing for screening for alpha-thalassemia-1 and beta-thalassemia traits

AIM: To evaluate the sensitivity, specificity, positive predictive value and negative predictive value of mean corpuscular volume (MCV) testing for screening for both alpha-thalassemia-1 and beta-thalassemia traits. METHODS: A diagnostic test was conducted on 439 pregnant women attending the antenatal care (ANC) clinic at Maharaj Nakorn Chiang Mai Hospital between April 2002 and July 2002. Blood samples were collected from the pregnant women after they were counseled and gave informed consent. The MCV was measured in all samples using an automated hematology analyzer. The hemoglobin (HbA2) level and polymerase chain reaction (PCR) were measured in all cases to test for the beta-thalassemia trait and the alpha-thalassemia-1 gene (South-East Asian [SEA] type), respectively. The data were collected and analyzed for sensitivity, specificity, positive predictive value and negative predictive value for evaluating the efficacy of MCV testing for screening for both alpha-thalassemia-1 and beta-thalassemia traits. RESULTS: Positive MCV tests (相似文献   

APC, β-catenin, and E-cadherin and the development of recurrent endometrial carcinoma

Endometrial carcinoma, generally, has a good prognosis. However, in some patients, the tumor appears to behave very aggressively, a course that cannot be explained with histopathological characteristics. More insight into the molecular background can be valuable to clarify these differences in tumor behavior. The three components associated with the Wnt pathway--i.e., adenomatous polyposis coli (APC), beta-catenin, and E-cadherin--were evaluated in a case-control study of 28 patients with stage-I endometrial carcinomas to determine their involvement in the development of recurrent disease. Mutation analysis of the mutation cluster region of the APC gene, determination of gene promoter methylation status of the APC-1A and E-cadherin genes, and immunohistochemical analysis of APC, E-cadherin, and beta-catenin were performed using paraffin-embedded tumor tissue. Twenty-one APC gene mutations were detected in 12 of 28 (43%) patients. Only three mutations would result in a stopcodon in the APC gene. APC gene promoter methylation was assessed in 12 of 28 (43%) patients. APC immunostaining was absent in two of 24 (8.3%) patients. The occurrence of APC mutations, APC gene promoter methylation, and APC immunostaining were not predictive for recurrence. No E-cadherin expression was observed in four of 24 patients (17%). E-cadherin gene promoter methylation could not be detected in any of the patients. The absence of E-cadherin expression was predictive for distant metastases, but not for local recurrence. Nuclear localization of beta-catenin was present in nine of 24 (38%) patients and was not predictive for recurrent disease. Involvement of epigenetic and genetic aberrations in APC and beta-catenin genes seems to be of minor importance for the development of local recurrences and distant metastases. Although the number of patients is limited, E-cadherin expression appears to be predictive for the development of distant metastases in endometrial carcinoma.     

A quality assessment tool to evaluate tocolytic studies

Over the past 15 years, the use of β-agonists has declined worldwide. Following the Royal College of Obstetricians and Gynaecologists guidelines in 2002, clinicians in the UK and beyond were faced with the dilemma of continuing to use β-agonists, desist from using tocolytic therapy completely or choosing to change to atosiban or calcium channel blockers (CCBs). While grade A level 1 evidence exists to show that atosiban is significantly more efficacious than placebo and significantly safer than β-agonists for the treatment of spontaneous preterm labour, the evidence for CCBs, such as nifedipine, is much less robust and no placebo-controlled trials have been performed. Published studies on nifedipine are largely investigator-led studies of small sample size, which lack sufficient power. As a result, most of the evidence has been based on meta-analyses of these studies, which look retrospectively at pooled data and are only as good as the quality of the studies included. In light of this, a tool was developed to produce a systematic review of studies on tocolytic effectiveness, which can and should be applied to all tocolytics and which considered both method- and topic-specific markers of quality. In the process of applying this tool to nifedipine, an extensive literature search identified 31 studies for a systematic review of the quality of nifedipine studies assessed by eight paired reviewers with wide experience in the subject of spontaneous preterm labour and preterm birth. Forty topic- and method-specific items of quality were assessed. The paucity of good quality studies of nifedipine used for the treatment of spontaneous preterm labour should be highlighted in meta-analyses or systematic reviews, which measure efficacy and should limit and influence the degree to which recommendations and guidelines are made on the basis of such studies.     

Influence of alpha-tumor necrosis factor and beta-interleukin-1 on production of angiogenetic factors and thymidine phosphorylase activity in immortalized human decidual fibroblasts in vitro

AIM: The aim of the present study was to investigate regulatory mechanisms of angiogenesis in the decidua using immortalized human decidual fibroblasts. METHODS: A sample of decidual fibroblasts was taken from a woman in early pregnancy. A cell line, DE-1, was established by infecting the decidual fibroblasts with the simian virus 40 large T antigen. Using this cell line, the ability to produce vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), beta-transforming growth factor (TGF-beta), and thymidine phosphorylase (TP) activity was investigated using immunohistochemistry, and the influences of beta-interleukin-1 (IL-1beta) and alpha-tumor necrosis factor (TNF-alpha) on these angiogenetic factors was investigated using enzyme-linked immunosorbent assays. Furthermore, the effects of TNF-alpha on proliferative capacity and apoptosis induction in DE-1 were studied. RESULTS: It was demonstrated that DE-1 produced all of these angiogenetic factors. The production of VEGF, bFGF and TGF-beta respectively was enhanced by both IL-1beta and TNF-alpha. TP activity was increased by TNF-alpha, but no increase was observed as a result of IL-1beta. It was shown that TNF-alpha suppressed the proliferation of DE-1 cells and significantly increased the percentage of apoptotic cells. CONCLUSION: It is suggested that IL-1beta and TNF-alpha stimulate decidual fibroblasts to up-regulate angiogenesis in the human decidua.     

Effect of inhaled glucocorticoid treatment on placental 11beta-hydroxysteroid dehydrogenase type 2 activity and neonatal birthweight in pregnancies complicated by asthma

BACKGROUND: Asthma is a common disease affecting 12% of Australian women with 55% of women experiencing at least one exacerbation during pregnancy. Exacerbations during pregnancy are associated with low birthweight neonates and stillbirth. One of the main reasons for maternal exacerbations during pregnancy is non-compliance with inhaled glucocorticoid treatment due to the misconception that inhaled glucocorticoids are harmful to the fetus. AIMS AND METHODS: We have therefore assessed whether the commonly used inhaled glucocorticoids reduce placental glucocorticoid metabolising capacity, by measuring 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD-2) activity. As these treatments potentially increase the exposure of the fetus to the growth-inhibiting effects of glucocorticoids, we also examined the question of whether inhaled glucocorticoid use was associated with reduced birthweight. Pregnant women using budesonide (n = 18), fluticasone propionate alone (n = 14) and fluticasone propionate in combination with the long-acting beta2 agonist salmeterol (n = 9) were compared to a non-asthmatic control group (n = 20). RESULTS: The use of inhaled budesonide was associated with significantly increased placental 11beta-HSD-2 activity relative to the control group. Inhaled glucocorticoid use for the treatment of asthma was associated with normal birthweight. In the small number of women using combination therapy (fluticasone and salmeterol), there was reduced birthweight compared to the control group. CONCLUSION: Inhaled glucocorticoids alone do not adversely affect fetal growth and placental function.     

Antiphosphatidyl serine antibodies are more common in normotensive women with small for gestational age pregnancies

BACKGROUND: Small for gestational age (SGA) babies are more common in women with antiphospholipid antibodies but data are limited about the prevalence of antiphospholipid antibodies in women who have delivered SGA babies. AIM: To determine whether elevated levels of anticardiolipin, antiphosphatidyl serine and/or antibeta2 glycoprotein I antibodies are more common in normotensive women who delivered SGA babies compared with women who delivered appropriate for gestational age babies. METHODS: Case-control study. Cases were normotensive women who delivered an SGA baby (birthweight <10th%) without chromosomal or congenital abnormality. Controls were healthy women who delivered a baby at term with birthweight >10th percentage. RESULTS: A total of 137 women with SGA pregnancies and 290 controls had antiphospholipid antibodies measured. The prevalence of anticardiolipin and antibeta2 glycoprotein I antibodies did not differ between SGA cases and controls. Antiphosphatidyl serine IgG antibodies were more common in women with SGA pregnancies than controls seven (5%) versus five (1.7%), relative risk (RR) 1.84 (1.12-3.03). There was no difference in the prevalence of 'any antiphospholipid antibodies' between SGA 10 (7.2%) and controls 16 (5.6%). There was a trend to more abnormal umbilical Doppler studies in SGA pregnancies with positive antiphospholipid antibodies three (50%) versus 19 (24%), RR 2.9 (0.62-13). CONCLUSIONS: Antiphospholipid antibodies were uncommon in this cohort of SGA pregnancies. Further studies are needed in SGA pregnancies with abnormal umbilical Doppler studies to determine if screening for antiphospholipid antibodies is worthwhile in this severe subgroup.     

The effect of cigarette or sheesha smoking on first-trimester markers of Down syndrome

Objective  To investigate the influence of cigarette or sheesha smoking on first-trimester markers of Down syndrome.
Design  A prospective observational study.
Setting  Primary care centres and antenatal clinics of Maternity and Children Hospital, King Abdulaziz University Hospital and New Jeddah Clinic Hospital, Jeddah, Saudi Arabia.
Population  Women with a singleton pregnancy who were either nonsmokers ( n = 1736) or cigarette smokers ( n = 420) or sheesha smokers ( n = 181).
Methods  Fetal nuchal translucency thickness (fetal NT), maternal serum free beta-human chorionic gonadotrophin (free β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) were measured at 11 weeks 0 days to 13 weeks 6 days of gestation in all women. Women were grouped according to smoking status, confirmed by maternal serum cotinine measurements, and analyte levels between groups were compared.
Main outcome measures  Fetal NT, maternal serum free β-hCG, PAPP-A and cotinine measurements.
Results  Compared with nonsmoking women, fetal NT was significantly increased and free β-hCG and PAPP-A levels were significantly decreased in both cigarette and sheesha smokers. There were significant relationships between all three markers and the number of sheeshas consumed per day.
Conclusions  Cigarette and sheesha smoking significantly affect first-trimester markers of Down syndrome (fetal NT, free β-hCG and PAPP-A). Correction for this effect in women who smoke might improve the effectiveness of first-trimester screening for Down syndrome in these women. The underlying mechanism(s) relating smoking to the changes in first-trimester markers require further studies.     

JSOG Best Paper Award 2002: 4

The aim of this study is to clarify the mechanism of bone formation by using 17β-estradiol (E2) during rat bone marrow stromal cell culture. Stromal cells were separated from female rat femora (seven weeks old), and were cultured in an Eagle Minimal Essential Medium (MEM) containing 15% fetal calf serum (FCS). After confluence, the cells were subcultured in a MEM containing 15% FCS (sex steroids removed by charcoal treatment) with dexamethasone, Na betaglycerophosphate and ascorbic acid phosphate for 18 days. They were then cultured in medium containing E2 or insulin-like growth factor-Ι (IGF-Ι) alone or with anti-IGF-Ι antibody. On the 14th day, the formation of white colored nodules showing positive ALP activity in ALP staining and showing calcium deposition in alizarin red S staining was observed in each culture system, indicating the beginning of calcification. The addition of E2 (10⁻⁷M or 10⁻⁸M), or IGF-Ι (10 and 100 ng/ml) enhanced ALP activity and calcium content significantly, but 17α-estradiol did not. Anti-IGF-Ι antibody significantly inhibited enhancing effects of E2 and IGF-Ι on ALP activity and calcium deposition. Incubating with E2 alone (10⁻⁸M), the medium IGF-Ι concentration and IGF-I mRNA expression in the cells were significantly increased on days 10~14, but the expression of IGF-Ι receptor mRNA had not changed. These results suggest that E2 participates in bone formation by promoting IGF-Ι production in the bone marrow stromal cells just before calcification starts.     

Antioxidant supplementation of culture medium during embryo development and/or after vitrification-warming; which is the most important?

Purpose  To determine the most optimal stage for antioxidant supplementation of culture medium to improve developmental competence, cryotolerance and DNA-fragmentation of bovine embryos. Methods  Presumptive zygotes were first cultured in presence or absence of β-mercaptoethanol (β-ME), for 8 days. Subsequently, half of the expanded blastocysts developed in both groups were vitrified, warmed within 30 min and post-warming embryos along with their corresponding non-vitrified embryos were cultured for two further days in presence or absence of (100 μM) βME. Results  For vitrified and non-vitrified embryos, the best effect was found when βME was added from day 1 of in vitro culture in continuation with post-warming culture period. Day 1–8 supplementation significantly increased the rates of cleavage, day 7 and day 8 blastocyst production. For non-vitrified embryos, βME addition during day 1–8 and/or 9–10 of embryo culture improved both hatching rate and quality of hatched embryos. For vitrified embryos, however, the percentage of DNA-fragmentation (18.5%) was significantly higher (p ≤ 0.05) than that of embryos developed in absence of βME but supplemented with βME during post-warming period (13.5%). Conclusions  Exogenous antioxidant increases the chance of embryos, even those of fair-quality, to develop to blastocyst. However, antioxidant inclusion during in vitro embryo development is not sufficient to maintain the redox state of these embryos during the critical period of post-warming embryo culture, and therefore, there should be a surplus source of exogenous antioxidant during post-warming embryo culture.     

Concentration of vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1) in the serum of patients with cervical cancer: prediction of response

Abstract. Moon H-S, Kim SC, Ahn JJ, Woo BH. Concentration of vascular endothelial growth factor (EGF) and transforming growth factor β-1 (TGF-β1) in the serum of patients with cervical cancer.
The aim of this study was to determine the value of the measurement of serum VEGF and TGF-β1 levels in the diagnosis of cervical cancer and to see whether these levels decrease after treatment for cervical cancer.
We measured serum VEGF and TGF-β1 levels through EIA in patients with CIN ( n = 35), and cervical squamous cell cancer ( n = 48). We also measured serum VEGF, TGF-β1, and SCC antigen levels before and after radiotherapy in 13 cervical squamous cell cancer patients. The sizes of the tumors in those patients were measured by a computer tomography scan or magnetic resonance imaging.
The serum VEGF levels were different between CIN and cervical cancer groups ( P < 0.1), and the serum TGF-β 1 levels in the cervical cancer group were lower than those in the other groups ( P < 0.05). The serum VEGF levels were significantly related to the serum TGF-β 1 levels in the cervical cancer patients ( P < 0.01). In the cervical cancer patients, the decrease in the circulating VEGF levels after receiving radiotherapy was related to the decrease in tumor size ( P < 0.01).
While the measurement of serum VEGF level is adjuvant in diagnosing cervical cancers, serial serum VEGF level measurements may find a clinical use in the follow-up of women treated for cervical cancer.     

Oral dehydroepiandrosterone restores ß-endorphin response to OGTT in early and late postmenopause

ß-endorphin is a neuropeptide involved in several brain functions: its plasma levels are higher in obese women and its release increases after oral glucose tolerance test (OGTT) in normal or obese women. The study included 46 healthy women and evaluated the effect of oral dehydroepiandrosterone [DHEA] (50?mg/day) in early postmenopausal women (50–55 years) both of normal weight (group A, n?=?12, BMI = 22.1?±?0.5) and overweight (group B, n?=?12, BMI = 28.2?±?0.5), and late postmenopausal women (60–65 years) both normal weight (group C, n?=?11, BMI = 22.5?±?0.6) and overweight (group D, n?=?11, BMI = 27.9?±?0.4) undergone OGTT, in order to investigate if DHEA could restore/modify the control of insulin and glucose secretion and ß-endorphin release in response to glucose load. The area under the curve (AUC) of OGTT evaluated plasma levels of different molecules. DHEA, DHEAS, and ß-endorphin plasma levels were lower in baseline conditions in older women than younger women. Considering the AUC of ß-endorphin response to OGTT, all groups showed a progressive significant increase after 3 and also after 6 months of treatment in comparison to baseline and 3 months of treatment.     

Úlcera vulvar de Lipschütz: comunicación de 2 casos y revisión de la literatura

Vulvar ulcer of Lipschütz it is an uncommon form of painful genital ulceration that appears in female children or adolescents and that is self-limited with fever, and systemic and flu-like symptoms. Its diagnosis is fundamentally clinical and through ruling out other more common reasons for genital ulcers. It is important to be familiar with this condition to be able to properly diagnose it, since most cases tend to resolve spontaneously. We present two new cases in girls with this condition.     

Effect of androgen substrates on the steroidogenic pattern of cumulus cells: Correlation with cumulus culture morphology

Background: In previous studies, higher progesterone secretion was observed in mature versus immature cumulusoocyte complexes. In mature cumulus mass that become homogeneously spread in culture (type C/D) progesterone secretion was higher than in partially (type B) or totally (type A) aggregated morphology. In sharp contrast, estradiol-17β secretion was significantly higher in type A than type C/D cumulus. Purpose: Our purpose was to assess whether the decreased estradiol-17β level in type C/D cumulus culture is caused by deficiency of substrates. Methods: The different cumulus types were incubated with or without 10⁻⁷ M dehydroepiandrosterone, 4-androstane-3, 17-dione, or testosterone. The levels of estradiol-17β, testosterone, and progesterone, were measured after 24 hr of culture. Results: The addition of dehydroepiandrosterone or 4-androstane-3,17-dione significantly increased the estradiol-17β levels in all types of cumulus cells, whereas the addition of testosterone was less effective. In all types of cumulus cells the testosterone levels increased significantly on adding these androgen substrates. In the type C/D cumulus, the testosterone increased to lower levels compared to type A cumulus cells. In the presence of these androgens progesterone secretion is significantly reduced in type A cumulus cells. In type C/D cumulus cells, however, progesterone levels were significantly higher than in type A. The estradiol-17β/testosterone and progesterone/estradiol-17β ratios, which partially resemble the degree of aromatase activity and the degree of selectivity for progesterone secretion, respectively, were higher in type C/D than in type A cumulus cells. Conclusions: In type C/D cumulus the significant increase in estradiol-17β secretion in the presence of various androgens suggests that, under basal conditions, androgen is less available for estradiol-17β biosynthesis compared to type A cumulus. Furthermore, the higher progesterone secretion in type C/D cumulus may suggest that the follicles yielding type C/D cumulus cells are more mature than the follicles yielding type A cumulus.     

Decrease in lipid levels of syncytiotrophoblast micro-particles reduced their potential to inhibit endothelial cell proliferation

Background Preeclampsia is characterized by damage to the maternal endothelium that has been suggested to be mediated in part by elevated shedding of inflammatory placental syncytiotrophoblast micro-particles (STBM) into the maternal circulation. Previously, we have shown that STBM, prepared by three different methods: mechanical dissection, in vitro placental explants culture and perfusion of placenta, can inhibit endothelial cell proliferation. Only mechanically prepared STBM induced apoptosis in the endothelial cells. Now, we have examined lipid levels in the three STBM preparations and their differential responses on endothelial cells. Methods We examined the lipid levels in the three STBM preparations using thin layer chromatography. Furthermore, the effects of reduced lipid levels in the three STBM preparations using the pharmacological agent methyl-β-cyclodextrin were examined on endothelial cell proliferation and apoptosis. Results Among the three STBM preparations, mechanical STBM contained highest levels of lipids. The reduction in lipid levels in mechanical STBM reduced their potential to inhibit human umbilical vein endothelial cells (HUVEC) proliferation and blocked their potential to induce apoptosis. No similar effect was observed following lipid reduction in the two other STBM preparations. Conclusions As it has been suggested that mechanically derived STBM may more closely resemble placental micro-particles generated in preeclampsia, our data suggest that lipid content may play a role in the anti-endothelial defects present in this disease.