Association between a functional polymorphism in the progesterone receptor gene and panic disorder in women

Although genetic factors are known to be important risk factors for panic disorder there is as yet no conclusive data regarding specific gene variants. Prompted by evidence supporting progesterone to influence the pathophysiology of panic disorder, polymorphisms in the progesterone receptor gene, a single nucleotide polymorphism (G331A) and an insertion/deletion polymorphism (PROGINS) were investigated in 72 patients with panic disorder and 452 controls. The frequency of the A-allele of the G331A polymorphism was higher in panic disorder patients than in controls (p = 0.01). When male and female patients were analyzed separately, the association was observed in female patients only (p = 0.0009), with an odds ratio of 3.5. No differences between groups were observed for the PROGINS polymorphism. In conclusion, these data suggest that the G331A polymorphism in the progesterone receptor gene may influence the risk for panic disorder in women.     

Expression of matrix metalloproteinase-26 and tissue inhibitors of metalloproteinases TIMP-3 and -4 in benign endometrium and endometrial cancer

OBJECTIVE: Matrix metalloproteinases (MMPs) and their physiological inhibitors, the tissue inhibitors of MMPs (TIMPs), play a key role in tumor cell invasion, angiogenesis, and growth. The aim of this study was to determine the expression and cellular distribution of MMP-26, TIMP-3, and TIMP-4 in endometrial cancers and benign endometrium throughout the menstrual cycle and the correlation with tumor histological subtype, stage, and grade. METHODS: Immunohistochemical analysis using polyclonal antibodies generated against pro- and active MMP-26, and mono- and polyclonal antibodies specific to TIMP-3 and TIMP-4, respectively, was performed. RESULTS: MMP-26, TIMP-3, and TIMP-4 are expressed in endometrial carcinomas (N = 86) and benign endometrium (N = 50) from various stages of the menstrual cycle. Semi-quantitative analysis of staining intensity indicated that endometrial carcinomas expressed more MMP-26, TIMP-3, and TIMP-4 compared to benign endometrium from the postmenopausal period, but not from the secretory phase of the menstrual cycle. The highest staining intensity was associated with endometrial epithelial cells, followed by vascular endothelial cells, myometrial smooth muscle cells, and endometrial stromal cells. Increased staining intensity of MMP-26 and TIMP-3 correlated with grade III tumors and MMP-26 and TIMP-4 with the depth of myometrial invasion in tumors histologically characterized as endometrioid adenocarcinoma, clear-cell, and papillary serous carcinoma staged/graded based on FIGO criteria. CONCLUSION: MMP-26 and TIMP-4 are expressed in endometrium and endometrial carcinoma and their elevated expression and correlation with myometrial invasion suggests that MMP-26 and TIMP-4 may play a key role in endometrial tumor progression.     

Cutaneous metastasis from carcinoma of the cervix at the drain site

BACKGROUND: Metastasis to the skin occurs rarely in gynecologic cancer, especially in cervical carcinoma. Although carcinoma of the cervix is the second to the fourth most common malignancy in women, cutaneous involvement originating from cervical cancer is particularly unusual, even in the terminal stage of the disease. CASE: We present a case of cervical cancer recurrence with skin metastasis. The extensive skin lesion on the abdominal wall occurred 4 years after radical surgery and postoperative radiotherapy. This was a biopsy-proven metastasis from the patient's primary cervical carcinoma. CONCLUSION: As far we know this is the second case (after Copas et al., Gynecol Oncol 1995;56:102-4) of skin and subcutaneous tissues metastasis from cervical carcinoma at the drain site. Palliative chemotherapy and radiotherapy have a useful role in controlling symptoms.     

Repeated doses of antenatal corticosteroids in animals: a systematic review

OBJECTIVE: The purpose of this review was to assess the effects of repeated doses of antenatal corticosteroids on lung and brain function and on growth restriction in animals. STUDY DESIGN: MEDLINE and EMBASE were searched for randomized controlled trials that compared repeated doses of antenatal corticosteroids versus a single dose, with or without placebo, in pregnant animals. RESULTS: Nineteen studies were included. The animals that were studied included sheep, monkeys, rabbits, and mice. There were 8 studies that assessed the effects of repeated doses of antenatal corticosteroids on lung function. All the studies reported improvement in lung function after repeated doses of antenatal corticosteroids. Seven studies investigated the effects of repeated doses of antenatal corticosteroids on brain or nervous system function or growth; all the studies found adverse effects with repeated doses of antenatal corticosteroids. Eleven studies looked at the effect of repeated doses of antenatal corticosteroids on fetal growth. Nine studies found evidence of fetal growth restriction with repeated doses of antenatal corticosteroids. One study assessed long-term behavioral outcomes in mice and found no effect. CONCLUSION: Evidence from randomized controlled trials in animals suggests that repeated doses of antenatal corticosteroids may have beneficial effects in terms of lung function but may have adverse effects on brain function and fetal growth. Because of the differences between animals and humans, it is difficult to extrapolate directly the results of these studies to humans. Therefore, randomized controlled trials in humans are needed to assess the effects of repeated courses of antenatal corticosteroids for pregnant women who are at increased risk of preterm birth in terms of important perinatal, neonatal, and maternal outcomes.     

Priming characteristics of peptide mimotopes of carbohydrate antigens

Immunization with peptide mimetics of carbohydrate antigens can induce functional carbohydrate-reactive antibodies. Here, we examine the immune characteristics of alternative approaches in prime and boost strategies using glycosylated HIV-1 envelope protein and model tumor associated carbohydrate antigens. Our results indicate that peptide mimotopes either in a DNA or carrier-conjugated format can induce comparable levels of IgM and IgG. Carbohydrate boosting of peptide-primed animals does not affect end-point titer, however, boosting mediates a stable long lasting carbohydrate reactive IgM response, not achievable by carbohydrate immunization alone. Boosting with carbohydrate in animals primed with DNA- or peptide-conjugate, facilitates the induction of detectable IgG with a dominant IgG2a isotype. Immunization with HIV-1 envelope glycoprotein of peptide-primed animals induces different IgG isotype profiles with a dominant IgG1 antibody. We observed that HIV-1 envelope glycoprotein immunization of peptide primed mice induces a cross-reactive cellular response, as detected by cytokine secretion, which lends to IFN-gamma production upon splenocyte stimulation and CTL activity against recombinant vaccinia virus infected cells after in vitro stimulation. DNA immunization with mimotope, inclusion of a T-cell epitope from the HIV-1 envelope protein in the expression cassette and co-administration with IL-12 or GM-CSF encoding plasmids activate a cellular response to the HIV-1 envelope protein.     

The CYP19 gene and associations with androgens and abdominal obesity in premenopausal women

OBJECTIVE: Elevated androgens in women are associated with type 2 diabetes and are dependent on the conversion to estrogens by aromatase cytochrome P450. Polymorphisms of a tetranucleotide repeat [TTTA](n) in the fourth intron of the CYP19 gene are associated with endocrine-dependent diseases and were examined in relation to hormone levels and disease risk factors in premenopausal women. RESEARCH METHODS AND PROCEDURES: A population sample of women born in 1956 (n = 270) were genotyped for this polymorphism and the results set in relation to steroid hormones, including saliva cortisol, anthropometric variables, estimates of insulin, glucose and lipid metabolism, and blood pressure. RESULTS: Seven tetranucleotide repeat [TTTA](n) alleles were detected with allelic sizes of 168 to 195 bp, with a TCT deletion/insertion (168/171 bp) upstream of this microsatellite. Smoking was associated with elevated androgens (p = 0.005 to 0.019). Using the median (average stretch, 177.5 bp) as a dividing line, nonsmoking women with the shorter microsatellite had higher free testosterone (p = 0.018) and lower sex hormone binding globulin (p = 0.033). These differences were pronounced with the 168-bp allele. Such women were also characterized by a less-substantial decrease of morning cortisols ("unwinding"; p = 0.035) and central obesity (abdominal sagittal diameter, p = 0.049) and had waist/hip circumference ratios of borderline significance (p = 0.064). DISCUSSION: The results indicate that, in premenopausal women, a short microsatellite in the fourth intron of the CYP19 gene, caused by a TCT deletion upstream the [TTTA](n) tract, is associated with elevated androgens, perturbed regulation of the hypothalamic-pituitary-adrenal axis, and abdominal obesity.     

Colposcopic and histologic findings in women with a cytologic diagnosis of atypical squamous cells of undetermined significance

BACKGROUND: The optimal method for managing a patient diagnosed with atypical squamous cells of undetermined significance (ASCUS) has not yet been established. The interim guidelines published by the National Cancer Institute suggest that a patient should be referred for colposcopy after the second ASCUS diagnosis within 2 years. AIM: To assess the significance of ASCUS in predicting the presence of underlying squamous intraepithelial lesion (SIL) of the uterine cervix. STUDY POPULATION: Women undergoing colposcopy for ASCUS cytology at a teaching hospital in Tehran University, in the years 1998-2001, considered eligible to enter this retrospective study. RESULTS: Of the 266 patients who underwent colposcopy, 28 (11%) had low-grade squamous intraepithelial lesion (LSIL), 16 (6.3%) had high-grade squamous intraepithelial lesion (HSIL) two (0.8%) had squamous cell carcinoma (SCC), and 48 (18.8%) had flat condyloma. CONCLUSION: Atypical squamous cells of undetermined significance (ASCUS) on a cervical smear is a good marker for detecting underlying SIL and condyloma. Thus, immediate colposcopy and directed biopsy are appropriate follow-up procedures.     

The effect of lifestyle-based education to women and their husbands on the anxiety and depression during pregnancy: a randomized controlled trial

Objective: The aim of this study was to determine the effect of lifestyle-based education to women and their husbands on anxiety and depression during pregnancy.

Method: This controlled trial was conducted on 189 pregnant women. Participants were allocated into three groups through block randomization. In the first intervention group, both women and their husbands, and in the second one, only women received the lifestyle-based education. In the control group, women received only the routine care. Edinburgh depression and Spielberger anxiety questionnaires were completed at baseline and 8 weeks after it.

Results: Compared to the control group, significant reductions were observed in the scores of depression (adjusted difference: ?4.7; 95% CI: ?5.9 to ?3.4), state anxiety (?8.1; ?11.3 to ?4.9) and trait anxiety (?8.3; ?11.9 to ?5.0) in the first intervention group, and in the scores of depression (?2.9; ?4.1 to ?1.6), state anxiety (?4.3; ?7.5 to ?1.1) and trait anxiety (?5.5; 95% CI: ?8.7 to ?2.3) in the second intervention group. Comparing the two intervention groups, mean scores of depression and state anxiety were significantly lower in the first group.

Conclusion: Results suggested the positive effect of lifestyle education to women and their husbands on depression and anxiety during pregnancy.     

New 6(17)-epoxylathyrane diterpene: aellinane from Euphorbia aellenii induces apoptosis via mitochondrial pathway in ovarian cancer cell line

Euphorbia species have been used in traditional medicine in many countries for the treatment of cancer. This article aims to evaluate the capability of a new lathyrane diterpene isolated from Euphorbia aellenii to induce apoptosis in the Caov-4 cell line to determine the underlying mechanism of its anticancer effects. A new 6(17)-epoxylathyrane diterpenes: aellinane from Euphorbia aellenii was evaluated for viability of Caov-4 cells by MTT method. Apoptosis induction by lathyrane diterpene was confirmed by annexin V-FITC/PI staining, and caspase-6 activation. The Bcl2 and Bax protein content were detected by Western blot analysis. Finally, we employed the fluorescent ROS detection kit and fluorochrome JC-1 to determine ROS levels and loss of mitochondria membrane potential (ΔΨm) in Caov-4 cells, respectively. The results show that lathyrane diterpene has significant cytotoxic effect against Caov-4 cells. The IC50 value was 45?μM. Annexin V/propidium iodide (PI) staining and caspase-6 activity assay confirmed that lathyrane diterpene is able to induce apoptosis in Caov-4 cells. The results also demonstrate that lathyrane diterpene up-regulated Bax and down-regulated Bcl-2 proteins. Moreover, apoptotic effect of lathyrane diterpene was also related to ROS production and loss of mitochondrial membrane potential (ΔΨm). This study demonstrated that lathyrane diterpene has profound activity against Caov-4 cells. Analysis of apoptosis-related proteins revealed that lathyrane diterpene triggered the mitochondrion-mediated apoptosis pathway, which led to the loss of mitochondrial membrane potential (ΔΨm) and activation of caspase-6. Therefore, we believe that lathyrane diterpene might be a promising natural compound in ovarian cancer therapy.