Helena von Eye Corleta

The degree of cycle irregularity correlates with the grade of endocrine and metabolic disorders in PCOS patients

OBJECTIVE PCOS (polycystic ovarian syndrome) is a clinically heterogeneous endocrine disorder which affects up to 4-10% of women of reproductive age. A standardized definition is still difficult because of a huge variety of different phenotypes. The aim of this study was to evaluate possible correlations between the degree of cycle irregularity and the grade of endocrine and metabolic abnormalities. STUDY DESIGN A cross-sectional study was carried out. Hyperandrogenic and/or hirsute women with regular menstrual cycles and polycystic ovaries on ultrasound (PCOS eumenorr, n=45), PCOS patients with oligomenorrhea (PCOS oligo, n=42) and PCOS patients with amenorrhea (PCOS amenorr, n=31) were recruited from the Department of Gynecological Endocrinology and Reproductive Medicine of the Womens University Hospital Heidelberg (Heidelberg, Germany). RESULTS Normocyclic patients demonstrated significantly better metabolic parameters (BMI, fasting insulin, HOMA-IR) than patients with oligo/amenorrhea. Hormonal parameters (LH, FSH, FAI and testosterone) were significantly different between patients with different menstrual patterns and patients with regular cycles. CONCLUSION Determining the degree of cycle irregularity as a simple clinical parameter might be a valuable instrument to estimate the degree of metabolic and endocrine disorders. Emphasis should be given to those parameters as a first step to characterize PCOS patients with a risk of endocrine and metabolic disorders leading to consequent detailed examination.

Risk factors for cardiovascular disease ten years after preeclampsia

CONTEXT AND OBJECTIVE Preeclampsia is a gestational disease that occurs mainly among nulliparous women after the 20th week of gestation, and frequently close to delivery. The effects of preeclampsia on womens blood pressure over the long term are still controversial. Patients with recurrent preeclampsia or preeclampsia in the early stages of pregnancy appear to present higher risk of hypertension. The aim of this study was to determine the risk factors for cardiovascular disease among women with preeclampsia 10 years earlier. DESIGN AND SETTING Cross-sectional study at Hospital de Clínicas de Porto Alegre (HCPA). METHODS Forty women with preeclampsia and 14 normotensive pregnant women followed up 10 or more years earlier at HCPA underwent clinical and laboratory examinations. Spearmans correlation coefficient was used to correlate body mass index (BMI) and systolic and diastolic pressures. The risk of developing hypertension was measured using the chi-square test. P < 0.05 was considered significant. RESULTS The patients with preeclampsia 10 or more years earlier had significantly higher diastolic blood pressure (P = 0.047), BMI (P = 0.019) and abdominal circumference (P = 0.026). They presented positive correlations between BMI and diastolic blood pressure (0.341; P = 0.031) and between BMI and systolic blood pressure (0.407; P = 0.009). CONCLUSION The patients with preeclampsia 10 or more years earlier had significantly higher diastolic blood pressure, BMI and abdominal circumference than did the control group. This emphasizes the importance of long-term follow-up assessment for cardiovascular risk factors among patients with preeclampsia.

Protein Expression of Estrogen Receptors α and β and Aromatase in Myometrium and Uterine Leiomyoma

Background: Leiomyomas are the most common tumors of the female reproductive tract and a major public health problem. The mechanism of tumorigenesis is unknown, but evidence suggests that estrogens regulate cell proliferation and myoma growth. This effect might be due to different amounts of estrogen receptors (ERα and ERβ) in normal and myoma tissues and overexpression of aromatase P450 in myomas. Purpose: To assess protein expression of ERs and aromatase in leiomyomas and normal adjacent myometrium of premenopausal women. Methods: Samples were collected from 12 premenopausal women admitted for abdominal hysterectomy due to fibroids. Results: The protein expression of ERα, ERβ and aromatase was similar in leiomyoma and normal myometrium (p = 0.239, p = 0.695 and p = 0.203, respectively). Conclusions: In this analysis of 12 matched leiomyoma and myometrial samples, the data do not support the theory that overexpression ERα, ERβ and aromatase in uterine leiomyomas compared to adjacent myometrium are the cause of tumor growth. The estrogens may exert their growth-stimulatory effects on leiomyomas intermediated by other elements, such as cytokines and growth or apoptosis factors. The effect of estrogen on the growth and development of fibroids is complex and far from being completely understood.

Immediate ureterovaginal fistula secondary to oocyte retrieval--a case report.

OBJECTIVE To report a case of ureterovaginal fistula secondary to transvaginal oocyte retrieval (TVOR). DESIGN Case report. SETTING IVF Center IN a private hospital. PATIENT(S) A 31-year-old woman presented immediately after TVOR with right lower abdominal pain with irradiation to the suprapubic area and vaginal discharge. INTERVENTION(S) Vaginal examination, creatinine dosage in plasma and vaginal discharge, excretory urography. A double-J catheter was inserted under general anesthesia. MAIN OUTCOME MEASURE(S) Clinical follow-up. RESULT(S) Vaginal leakage ceased a few hours after catheter insertion. Transfer of two embryos was performed 3 days after TVOR, but no pregnancy occurred. The double-J catheter was removed 21 days after its placement. Imaging studies done 6 weeks later demonstrated a normal urinary tract morphology. CONCLUSION(S) Given the elective nature of TVOR and IVF, patients should be informed about all potential complications, including ureterovaginal fistula.

Insulin-Like Growth Factor 1 Receptor mRNA Expression and Autophosphorylation in Human Myometrium and Leiomyoma

Uterine leiomyomas are the most common tumors of the genital tract. Growth factors seem to be implicated in the development of leiomyoma. The aim of this study was to determine insulin-like growth factor 1 receptor (IGF-1-R) mRNA levels and IGF-1-R tyrosine kinase activity in normal myometrium and leiomyoma. Plasma membranes of myometrium and leiomyoma of 14 women subjected to hysterectomy were prepared, and samples were incubated in the absence or presence of recombinant human IGF-1 to assess the tyrosine kinase activity (Western blot). Reverse-transcriptase polymerase chain reaction with specific primers for IGF-1-R was used to determine IGF-1-R mRNA levels. IGF-1-R mRNA levels in myometrium (0.8216 ± 0.096) and in leiomyoma (0.7905 ± 0.136) were not statistically significantly different (p = 0.648). The degree of IGF-1-R autophosphorylation stimulated by recombinant IGF-1 was not different in myometrium (1.020 ± 0.120) and leiomyoma (1.620 ± 0.656) either (p = 0.075). There was no difference in IGF-1-R expression and IGF-1-R autophosphorylation between normal myometrium and leiomyoma.

Biologia molecular do câncer cervical

Carcinogenesis involves several steps. Disorders of the cytogenetic balance occur during the evolution from normal epithelium to cervical cancer. Several studies support the hypothesis that the Human Papiloma Virus (HPV) infection is associated to development of premalignant and malignant lesions of cervical cancer. In this review we show the basis to understand cervical oncogenesis. The cell cycle is controlled by protooncogenes and supressive genes. This orchestrated cell cycle can be affected by virus such as HPV. Of special interest in the cervical carcinogenesis are the HPV subtypes 16 and 18. How HPV immortalizes cervical cells is not fully understood. Advances have been made in the application of molecular biology techniques in the understanding of this mechanism. Once established, these techniques will lead to a better assessment of cervical neoplasias and help the development of new therapies, hopefully less invasive and more effective.

Metformin modulates PI3K and GLUT4 expression and Akt/PKB phosphorylation in human endometrial stromal cells after stimulation with androgen and insulin

OBJECTIVE To assess the effect of metformin on expression of Akt, ERK, PI3K and GLUT4, proteins associated with the growth factor signaling cascade, in human endometrial stromal cells after stimulation with androgen and insulin. STUDY DESIGN Primary culture of endometrial stromal cells were stimulated in different groups with estrogen, progesterone, androgen and insulin and treated with metformin for 10min, 24h and 48h. After 14 days, proteins were extracted for Western blot analysis. RESULTS PI3K and GLUT4 expression were increased in the insulin-treated group and further attenuated when metformin was added. The ERK protein was not affected, whereas the Akt phosphorylation was significantly decreased by the action of metformin. CONCLUSION Metformin affects human endometrial stromal cells by acting on proteins related to growth factors, usually increasing their expression when combined with insulin. Akt phosphorylation was inhibited by metformin, possibly due to its anti-proliferative action.

Cycle modulation of insulin-like growth factor-binding protein 1 in human endometrium

Endometrium is one of the fastest growing human tissues. Sex hormones, estrogen and progesterone, in interaction with several growth factors, control its growth and differentiation. Insulin-like growth factor 1 (IGF-1) interacts with cell surface receptors and also with specific soluble binding proteins. IGF-binding proteins (IGF-BP) have been shown to modulate IGF-1 action. Of six known isoforms, IGF-BP-1 has been characterized as a marker produced by endometrial stromal cells in the late secretory phase and in the decidua. In the current study, IGF-1-BP concentration and affinity in the proliferative and secretory phase of the menstrual cycle were measured. Endometrial samples were from patients of reproductive age with regular menstrual cycles and taking no steroid hormones. Cytosolic fractions were prepared and binding of (125)I-labeled IGF-1 performed. Cross-linking reaction products were analyzed by SDS-polyacrylamide gel electrophoresis (7.5%) followed by autoradiography. (125)I-IGF-1 affinity to cytosolic proteins was not statistically different between the proliferative and secretory endometrium. An approximately 35-kDa binding protein was identified when (125)I-IGF-1 was cross-linked to cytosol proteins. Secretory endometrium had significantly more IGF-1-BP when compared to proliferative endometrium. The specificity of the cross-linking process was evaluated by the addition of 100 nM unlabeled IGF-1 or insulin. Unlabeled IGF-1 totally abolished the radioactivity from the band, indicating specific binding. Insulin had no apparent effect on the intensity of the labeled band. These results suggest that IGF-BP could modulate the action of IGF-1 throughout the menstrual cycle. It would be interesting to study this binding protein in other pathologic conditions of the endometrium such as adenocarcinomas and hyperplasia.

Prevalence of abnormal anal cytology in women infected with HIV

Anal cancer is a rare disease. Nevertheless, it may be a reason for concern among groups in which its incidence is increasing: those who engage in anoreceptive intercourse, promiscuous persons, and those with sexually transmitted infections (HPV and HIV). The aim of this study was to evaluate the prevalence of abnormal anal cytology in women infected with HIV seen at Hospital de Clínicas de Porto Alegre, Brazil. A cross‐sectional design was used. Anal smear screening was offered to all women infected with HIV seen at the hospitals outpatient sexually transmitted infections clinic from March 2006 to March 2008. A total of 184 patients were thus enrolled. Only patients who gave written consent were included in the study. The prevalence of abnormal anal cytology was 14.1% (26 patients). Twenty‐two patients presented atypical squamous cells of undetermined significance, and four exhibited low‐grade intraepithelial neoplasia. Initially, abnormal anal cytology was significantly associated with age, number of pregnancies, smoking, abnormal cervical cytology, CD4+ < 200 cells/mm3 and hepatitis C co‐infection. After adjustment, only CD4+ < 200 cells/mm3 and smoking were found to increase the risk of altered anal cytology. The anal Pap method described is simple and can be used for screening in cohorts of HIV‐positive women who are at risk of developing anal carcinoma, mainly those with CD4+ counts <200 cells/mm3 and smokers. J. Med. Virol. 84:1335–1339, 2012.

Does metformin influence the insulin-, IGF I- and IGF II-receptor gene expression and Akt phosphorylation in human decidualized endometrial stromal cells?

OBJECTIVE To assess the effects of metformin on insulin-, IGF I-, and IGF II-receptor gene expression and Akt phosphorylation in decidualized human endometrial stromal cells (ESC) after stimulation with insulin, IGF I and II. STUDY DESIGN ESC were isolated from healthy, regularly cycling women and after two passages decidualized with estrogen/progesterone±metformin. Cells were incubated with insulin, IGF I or IGF II for 1, 5, and 10 min to assess Akt phosphorylation by Western blot. To investigate the insulin-, IGF I- and IGF II-receptor gene expression ESC were incubated with insulin, IGF I or IGF II for 6 and 24h. RESULTS Insulin- and IGF I-receptor gene expression in ESC changed significantly after incubation with insulin, IGF I or IGF II. This was further augmented in metformin pretreated cells, while IGF II-receptor gene expression changed particularly after pretreatment with metformin. Akt phosphorylation peaked after 5 min insulin, IGF I and IGF II stimulation in ESC in both control (control 0.08 ± 0.03 vs. insulin 0.74 ± 0.19, IGF I 0.68 ± 0.22, IGF II 0.53 ± 0.13, p<0.05) and metformin pretreated cells (control 0.03 ± 0.01 vs. insulin 0.75 ± 0.11, IGF I 0.74 ± 0.15, IGF II 0.67 ± 0.09, p<0.005). However, there was no significant difference between the control and metformin pretreated group. CONCLUSION Insulin, IGF I and IGF II lead to changes in their receptor gene expression and induced Akt phosphorylation in ESC. These effects were further highlighted in the presence of metformin.