The effect of GnRH-a on the angiogenesis of endometriosis.

PURPOSE: Neoangiogenesis is necessary for adhesion and invasiveness of endometriotic lesions in women affected by endometriosis. Vascular endothelial growth factor (VEGF) is one of the main components of angiogenesis and is part of the major pathway tissue factor (TF)-protease activated receptor-2 (PAR-2)-VEGF that leads to neoangiogenesis. Specificity protein 1 (SP1) is a transcriptional factor that has recently been studied for its crucial role in angiogenesis via a specific pathway. We hypothesize that by blocking angiogenetic pathways we can suppress endometriotic lesions. Gonadotrophin-releasing hormone-agonists (GnRH-a) are routinely used, especially preoperatively, in endometriosis. It would be of great interest to clarify which angiogenetic pathways are affected and, thereby, pave the way for further research into antiangiogenetic effects on endometriosis. METHODS: We used quantitative real-time polymerase chain reaction (qRT-PCR) to study mRNA expression levels of TF, PAR-2, VEGF, and SP1 in endometriotic tissues of women who underwent surgery for endometriosis and received GnRH-a (leuprolide acetate) preoperatively. RESULTS: VEGF, TF, and PAR-2 expression is significantly lower in patients who received treatment (p < 0,001) compared to those who did not, whereas SP1 expression is not altered (p = 0.779). CONCLUSIONS: GnRH-a administration does affect some pathways of angiogenesis in endometriotic lesions, but not all of them. Therefore, supplementary treatments that affect the SP1 pathway of angiogenesis should be developed to enhance the antiangiogenetic effect of GnRH-a in patients with endometriosis. TRIAL REGISTRATION: Clinicaltrial.gov ID: NCT06106932.

Placental mRNA Expression of Neurokinin B Is Increased in PCOS Pregnancies with Female Offspring.

Current research suggests that polycystic ovary syndrome (PCOS) might originate in utero and implicates the placenta in its pathogenesis. Kisspeptin (KISS1) and neurokinin B (NKB) are produced by the placenta in high amounts, and they have been implicated in several pregnancy complications associated with placental dysfunction. However, their placental expression has not been studied in PCOS. We isolated mRNA after delivery from the placentae of 31 PCOS and 37 control women with term, uncomplicated, singleton pregnancies. The expression of KISS1, NKB, and neurokinin receptors 1, 2, and 3 was analyzed with real-time polymerase chain reaction, using ß-actin as the reference gene. Maternal serum and umbilical cord levels of total testosterone, sex hormone-binding globulin (SHBG), free androgen index (FAI), androstenedione, dehydroepiandrosterone sulfate (DHEAS), Anti-Mullerian hormone (AMH), and estradiol were also assessed. NKB placental mRNA expression was higher in PCOS women versus controls in pregnancies with female offspring. NKB expression depended on fetal gender, being higher in pregnancies with male fetuses, regardless of PCOS. NKB was positively correlated with umbilical cord FAI and AMH, and KISS1 was positively correlated with cord testosterone and FAI; there was also a strong positive correlation between NKB and KISS1 expression. Women with PCOS had higher serum AMH and FAI and lower SHBG than controls. Our findings indicate that NKB might be involved in the PCOS-related placental dysfunction and warrant further investigation. Studies assessing the placental expression of NKB should take fetal gender into consideration.

COVID-19 Pharmacotherapy in Pregnancy: A Literature Review of Current Therapeutic Choices.

The clinical management of COVID-19 in pregnant women, who are considered a vulnerable population, remains uncertain even as the pandemic subsides. SARS-CoV-2 affects pregnant individuals in multiple ways and has been associated with severe maternal morbidity and mortality, as well as neonatal complications. The unique anatomy and physiology of gestation make managing COVID-19 in this population a complex and challenging task, emphasizing the importance of spreading knowledge and expertise in this area. Therapeutic interventions require distinct clinical consideration, taking into account differences in pharmacokinetics, vertical transmission, drug toxicities, and postnatal care. Currently, there is limited data on antiviral and immunomodulating COVID-19 pharmacotherapy in pregnancy. Some medication has been shown to be safe and well tolerated among pregnant women with COVID-19; however, the lack of randomized clinical trials and studies in this patient population is evident. Available vaccines are considered safe and effective, with no evidence of harm to the fetus, embryo development, or short-term postnatal development. Pregnant women should be counseled about the risks of SARS-CoV-2 infection and informed of available ways to protect themselves and their families. Effective treatments for COVID-19 should not be withheld from pregnant individuals, and more research is needed to ensure the best outcomes.

Expression stability of ACTB, 18S, and GAPDH in human placental tissues from subjects with PCOS and controls: GAPDH expression is increased in PCOS.

PURPOSE: The aim was to assess the expression stability of three commonly used reference genes, namely, ß-actin (ACTB), 18S ribosomal RNA (18S), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), in placental tissue obtained from pregnant women with polycystic ovary syndrome (PCOS) and healthy controls. METHODS: mRNA was isolated after delivery from the placentae of 10 PCOS and 10 control women with term, uncomplicated, singleton pregnancies. The expression of ACTB, 18S, and GAPDH was analyzed using real-time polymerase chain reaction (RT-PCR). Gene expression stability was evaluated with the RefFinder, GeNorm, Normfinder, BestKeeper, and Delta-Ct tools. RESULTS: ACTB was ranked as the most stably expressed gene, followed by 18S. The expression of GAPDH varied considerably in both studied groups, while it was increased in PCOS versus controls (5.3-fold, p < 0.05). CONCLUSIONS: ACTB is an appropriate reference gene for placental gene expression studies in women with PCOS, whereas GAPDH is unfit for such a role, as its placental expression is increased in PCOS.

Wnt4, Wnt6 and ß-catenin expression in human placental tissue - is there a link with first trimester miscarriage? Results from a pilot study.

BACKGROUND: Demystifying the events around early pregnancy is challenging. A wide network of mediators and signaling cascades orchestrate the processes of implantation and trophoblast proliferation. Dysregulation of these pathways could be implicated in early pregnancy loss. There is accumulating evidence around the role of Wnt pathway in implantation and early pregnancy. The purpose of this study was to explore alterations in the expression of Wnt4, Wnt6 and ß-catenin in placental tissue obtained from human first trimester euploid miscarriages versus normally developing early pregnancies. METHODS: The study group consisted of first trimester miscarriages (early embryonic demises and incomplete miscarriages) and the control group of social terminations of pregnancy (TOPs). The placental mRNA expression of Wnt4, Wnt6 and ß-catenin was studied using reverse transcription PCR and real time PCR. Only euploid conceptions were included in the analysis. RESULTS: Wnt4 expression was significantly increased in placental tissue from first trimester miscarriages versus controls (p = 0.003). No significant difference was documented in the expression of Wnt6 (p = 0.286) and ß-catenin (p = 0.793). There was a 5.1fold increase in Wnt4 expression for early embryonic demises versus TOPs and a 7.6fold increase for incomplete miscarriages versus TOPs - no significant difference between the two subgroups of miscarriage (p = 0.533). CONCLUSIONS: This is, to our knowledge, the first study demonstrating significant alteration of Wnt4 expression in human placental tissue, from failed early pregnancies compared to normal controls. Undoubtedly, a more profound study is needed to confirm these preliminary findings and explore Wnt mediators as potential targets for strategies to predict and prevent miscarriage.

Teenage pregnancies in Western Greece: experience from a university hospital setting.

PURPOSE: Teenage pregnancies have consistently been associated with preterm labor in a wide range of studies. Evidence regarding the incidence and potential complications of teenage pregnancies in Greece is at present scarce. The aim of this study was to evaluate the perinatal outcomes as well as the risk of perinatal and obstetric complications of teenage pregnancies. METHODS: This retrospective study was conducted at the Department of Obstetrics and Gynecology of the University Hospital of Patras, Greece, and all data recorded concerned the year 2019 (January-December). We retrospectively reviewed 643 cases of singleton pregnancies divided into two groups, as follows: Group A included women of average maternal age (AMA) (20-34 years old), and Group B included teenagers, defined as women less than 20 years old. Data regarding demographic and pregnancy characteristics as well as obstetric and neonatal complications were collected. RESULTS: Teenage pregnancies accounted for 6.7% of all deliveries. We detected significantly higher rates of preterm births (p = 0.025), primiparity (p < 0.001), and negative marital status (p < 0.001) in teenage mothers compared to pregnant women of AMA. There were no significant differences concerning other factors between the two groups. CONCLUSIONS: The findings of the present study raise concern regarding the perinatal, obstetric, and social consequences of teenage pregnancies in Greece. Extended studies that will include further information on antenatal care and detailed socioeconomic factors (i.e., level of education, income, and ethnicity) are required to formulate reliable conclusions concerning teenage pregnancies and their effect on maternal and neonatal health.

Impaired Sexual Function in Young Women With PCOS: The Detrimental Effect of Anovulation.

BACKGROUND: Even though polycystic ovary syndrome (PCOS) is a common reproductive disorder affecting young women, its impact on their sexual health is not well known. AIM: To examine the different aspects of female sexuality in young women with PCOS and attempt to associate hormonal changes and ovulatory status with their sexual function. METHODS: Anthropometric characteristics, hormonal levels and sexual function based on the Female Sexual Function Index (FSFI) questionnaire were assessed in 76 young women with PCOS and 133 matched controls. OUTCOMES: Sexual function is significantly impaired in young women with PCOS. RESULTS: Women with PCOS demonstrated lower scores than controls in arousal (5.04 ± 1.19 vs 4.48 ± 1.44, P < .001), lubrication (5.29 ± 1.17 vs 4.69 ± 1.54, P < .001), orgasm (4.78 ± 1.40 vs 4.11 ± 1.61, P = .001), satisfaction (5.22 ± 1.10 vs 4.78 ± 1.31, P = .016), and total score of the FSFI (29.51 ± 5.83 vs 26.76 ± 6.81, P < .001), even after correction for BMI. When corrected for total testosterone, the domains of lubrication, satisfaction, and total score of FSFI remained significantly impaired in women with PCOS (P values .037, .024, & .044 respectively). In multivariate logistic regression analysis, after adjusting for the effect of BMI and hormone levels, dysfunction in orgasm, satisfaction and the total FSFI score were still 3-4 times more common in PCOS (adjusted OR [95% CI]: 3.54, P = .020; 2.96, P = .050; 3.87, P = .027). Even though no statistically significant differences were observed between women with ovulatory PCOS and controls, we detected statistically significant differences in all domains of sexual function apart from pain between controls and PCOS women with anovulation (desire P value .04, arousal P value <.001, lubrication P value <.001, orgasm P value .001, satisfaction P value .001 and FSFI total score P value <.001). CLINICAL IMPLICATIONS: Women with PCOS have compromised sexual function, which is independent of their BMI and highly dependent on their ovulatory status. STRENGTHS AND LIMITATIONS: This is the first study in women with PCOS that implicates anovulation as a risk factor for sexual impairment in PCOS. Further studies are needed to elucidate the mechanisms implicated and to examine the effect of PCOS therapy on the patients' sexual function. CONCLUSION: The adverse effect of PCOS status on the female sexual function is independent of BMI and only partially dependent on hormonal changes characterizing the syndrome. Anovulation appears to be the major determinant of sexual impairment among women with PCOS. Mantzou D, Stamou MI, Armeni AK, et al. Impaired Sexual Function in Young Women With PCOS: The Detrimental Effect of Anovulation. J Sex Med 2021;18:1872-1879.

The Effect of Novel Medical Nonhormonal Treatments on the Angiogenesis of Endometriotic Lesions.

IMPORTANCE: Irrespective of the precise mechanisms leading to endometriosis, angiogenesis is essential for the establishment and long-term proliferation of the disease. As current surgical and medical management options for women with endometriosis have substantial drawbacks and limitations, novel agents are needed and molecules targeting the angiogenic cascade could serve as potential candidates. OBJECTIVE: Our aim was to review current data about the role of angiogenesis in the pathophysiology of endometriosis and summarize the novel antiangiogenic agents that could be potentially used in clinical management of patients with endometriosis. EVIDENCE ACQUISITION: Original research and review articles were retrieved through a computerized literature search. RESULTS: Loss of balance between angiogenic activators and suppressors triggers the nonphysiological angiogenesis observed in endometriotic lesions. Several proangiogenic mediators have been identified and most of them have demonstrated increased concentrations in the peritoneal fluid and/or serum of women with endometriosis. Among the antiangiogenic molecules, anti-vascular endothelial growth factor agents, dopamine agonists, romidepsin, and statins have shown the most promising results so far. CONCLUSIONS AND RELEVANCE: Given the limitations of current treatments of endometriosis, there is a need for novel, more efficient agents. Antiangiogenic molecules could be used potentially in clinical management of women with endometriosis; however, their safety and efficiency should be carefully assessed prior to that. Further large prospective trials in humans are needed before any treatment is introduced into daily clinical practice.

The expression pattern of galectins during human epidermal morphogenesis.

INTRODUCTION: Galectins constitute a phylogenetically conserved family of proteins with high binding affinity for glycoconjugates bearing ß-galactoside residues. Surprisingly, knowledge of the expression pattern of galectins during human epidermal morphogenesis is very limited. METHODS: Fifty-eight biopsy skin specimens obtained from human embryos and 10 biopsy specimens obtained from healthy adult volunteers were processed for immunohistochemistry using a panel of antibodies against galectins 1, 3, 7, and 9. RESULTS: Fetal human epidermis was devoid of any galectin 1 immunoreactivity, whereas clear-cut changes were found in the galectin 3 immunoreactivity of fetal epidermis with advancing gestational age. The expression pattern of galectins 7 and 9 remained constant at all stages of gestation. CONCLUSIONS: The changes in galectin 3 immunoreactivity of human fetal epidermis with advancing gestational age, which are reported here for the first time, suggest that this galectin and its ligands may be implicated in the molecular events underlying human epidermal morphogenesis. It remains to be elucidated in future investigations whether the expression pattern of galectins, particularly that of galectin 3, in the developing human epidermis reveals alterations in fetuses with inherited cutaneous disorders that may be important for prenatal diagnosis of these disorders.

Acceptability of Self-Sampling for Human Papillomavirus-Based Cervical Cancer Screening.

Background: Human papillomavirus (HPV)-DNA testing combined with self-sampling could increase cervical cancer screening effectiveness, utilizing a sensitive screening modality and an easy sampling method with minimal pain or discomfort. Self-sampling acceptability, though, is pivotal. Materials and Methods: This study is a nested cross-sectional survey within GRECOSELF, a cross-sectional study on HPV-based screening with self-sampling, aiming at investigating self-sampling acceptability among Greek women residing in rural areas, and the factors affecting it. Women between 25 and 60 years old were recruited by midwives participating in a nationwide midwifery network. Participants, after self-sampling, filled out a questionnaire with three sections, one regarding demographic characteristics, a second with questions pertaining to the participants' cervical cancer screening history, and a third with questions regarding the self-sampling process per se. Results: The sample included 13,111 women. Most participants (67.9%), including those screened or not in the past, would prefer self-sampling if assured that the results are not inferior to standard testing. Discomfort or pain during self-sampling was absent or minimal in 97.1% and 96.5% of the cases, respectively, and 74.4% of the women felt adequately confident that they followed the instructions correctly. Women mostly preferred self-sampling at home compared with health care facilities. Pain and discomfort during the procedure, although rare, were significant factors against acceptance. Most of the women reporting a negative impression had a negative experience with conventional sampling in the past. Conclusion: Self-sampling is highly acceptable. Acceptance can be further improved with proper communication of the process and its noninferiority compared with conventional screening.

Ultralong administration of gonadotropin-releasing hormone agonists before in vitro fertilization improves fertilization rate but not clinical pregnancy rate in women with mild endometriosis: a prospective, randomized, controlled trial.

OBJECTIVE: To evaluate the effects of gonadotropin-releasing hormone agonists (GnRH-a) on fertility in women with mild endometriosis who are undergoing in vitro fertilization and embryo transfer (IVF-ET) procedures. DESIGN: Prospective, randomized, controlled trial. SETTING: Three tertiary university hospitals. PATIENT(S): Four hundred infertile women with mild endometriosis, documented with laparoscopy, undergoing IVF and 200 women with tubal factor infertility. INTERVENTION(S): Administration of GnRH-a for 3 months before an IVF attempt (group A, n = 200) or IVF without GnRH-a (group B, n = 200). MAIN OUTCOME MEASURE(S): Follicular fluid (FF) levels of tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), IL-6, IL-8, and IL-1 receptor antagonist; fertilization rate (FR), implantation rate (IR), quality of embryos, and clinical pregnancy rate (PR). RESULT(S): Women who received GnRH-a had a statistically significantly reduced concentration of FF cytokines compared with women who did not receive this regimen. Women in group B had a reduced FR (61.7; 95% CI, 59.20-64.20) compared with the women in group A (72.7; 95% CI, 70.50-74.90) and compared with the women with tubal factor infertility (74.7; 95% CI, 72.00-77.24). The embryo quality, IR, and clinical PR showed no statistically significant improvement in the women of group A compared with group B. CONCLUSION(S): Women who received GnRH-a for 3 months had a lower concentration of FF cytokines. These women had also a higher FR than the women who did not receive GnRH-a. However, the IR, embryo quality, and clinical PR showed no statistically significant difference when comparing the two groups. CLINICALTRIALS. GOV ID: NCT01269125.

Implementation of HPV-based Cervical Cancer Screening Combined with Self-sampling Using a Midwifery Network Across Rural Greece: The GRECOSELF Study.

Self-sampling for human papillomavirus (HPV) testing is an alternative to physician sampling particularly for cervical cancer screening nonattenders. The GRECOSELF study is a nationwide observational cross-sectional study aiming to suggest a way to implement HPV-DNA testing in conjunction with self-sampling for cervical cancer screening in Greece, utilizing a midwifery network. Women residing in remote areas of Greece were approached by midwives, of a nationwide network, and were provided with a self-collection kit (dry swab) for cervicovaginal sampling and asked to answer a questionnaire about their cervical cancer screening history. Each sample was tested for high-risk (hr) HPV with the Cobas HPV test. HrHPV-Positive women were referred to undergo colposcopy and, if needed, treatment according to colposcopy/biopsy results. Between May 2016 and November 2018, 13,111 women were recruited. Of these, 12,787 women gave valid answers in the study questionnaire and had valid HPV-DNA results; hrHPV prevalence was 8.3%; high-grade cervical/vaginal disease or cancer prevalence was 0.6%. HrHPV positivity rate decreased with age from 20.7% for women aged 25-29 years to 5.1% for women aged 50-60 years. Positive predictive value for hrHPV testing and for HPV16/18 genotyping ranged from 5.0% to 11.6% and from 11.8% to 27.0%, respectively, in different age groups. Compliance to colposcopy referral rate ranged from 68.6% (for women 25-29) to 76.3% (for women 40-49). For women residing in remote areas of Greece, the detection of hrHPV DNA with the Cobas HPV test, on self-collected cervicovaginal samples using dry cotton swabs, which are provided by visiting midwives, is a promising method for cervical cancer secondary prevention.

Pregnancy outcomes and nutritional indices after 3 types of bariatric surgery performed at a single institution.

BACKGROUND: Nutritional status during pregnancy and the effects of nutritional deficiencies on pregnancy outcomes after bariatric surgery is an important issue that warrants further study. The objective of this study was to investigate pregnancy outcomes and nutritional indices after restrictive and malabsorptive procedures. METHODS: We investigated pregnancy outcomes of 113 women who gave birth to 150 children after biliopancreatic diversion (BPD), Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG) between June 1994 and December 2011. Biochemical indices and pregnancy outcomes were compared among the different types of surgery and to overall 20-year hospital data, as well as to 56 presurgery pregnancies in 36 women of the same group. RESULTS: Anemia was observed in 24.2% and 15.6% of pregnancies after BPD and RYGB, respectively. Vitamin B12 levels decreased postoperatively in all groups, with no further decrease during pregnancy; however, low levels were observed not only after BPD (11.7%) and RYGB (15.6%), but also after SG (13.3%). Folic acid levels increased. Serum albumin levels decreased in all groups during pregnancy, but hypoproteinemia was seen only after BPD. Neonates after BPD had significantly lower average birth weight without a higher frequency of low birth weight defined as<2500 g. A comparison of neonatal data between babies born before surgery and siblings born after surgery (AS) showed that AS newborns had lower average birth weight with no significant differences in body length or head circumference and no cases of macrosomia. CONCLUSION: Our study showed reasonably good pregnancy outcomes in this sample population after all types of bariatric surgery provided nutritional supplement guidelines are followed. Closer monitoring is required in pregnancies after malabsorptive procedures especially regarding protein nutrition.

Hybrid transvaginal nephrectomy: development of our technique.

OBJECTIVE: To evaluate the development of natural orifice transluminal endoscopic surgery (NOTES) transvaginal nephrectomy and present the initial experience. METHODS: Thirty-eight female patients were submitted to hybrid NOTES transvaginal nephrectomy for tumor (n=23) and nonfunctioning renal unit (n=15) in 2 academic medical centers. Patients underwent surgery from July 2010 to June 2012 and none of them were candidates for partial nephrectomy (clinical stage T1b or higher). The procedure was performed by the use of multi-instrument ports or flexible cannulas inserted through umbilical and vaginal incisions. A 30° lens extra-long camera and combinations of conventional laparoscopic and prebent instruments were used. Specially designed extra-long, prebent straight instruments were found to be particularly useful for transvaginal manipulations. Prospective data regarding patient demographics, intraoperative and postoperative course of the patients, and pathology results were collected. RESULTS: Average tumor diameter was 6 cm (range, 4.9-7.5 cm). Average operative time was 114.1 minutes (range, 90-190 minutes). Estimated blood loss ranged between 50 and 150 mL (average, 80 mL). Intraoperatively, 2 bladder perforations occurred and were treated by suturing. Postoperatively, 2 patients suffered from fever of unknown origin and 2 patients required transfusions due to bleeding. Average hospital stay was 3.3 days (range, 3-5 days). Positive surgical margins were not detected. CONCLUSION: Hybrid NOTES transvaginal nephrectomy is a feasible and safe alternative to standard laparoscopic nephrectomy in selected patients. Difficulties arising from limitations in current instrumentation have been addressed by the use of specially designed instruments. Further clinical studies are required to ascertain this approaches' place among nephrectomy techniques.

Spontaneous uterine rupture in a primigravid woman in the early third trimester attributed to adenomyosis: a case report and review of the literature.

We report a rare case of spontaneous uterine rupture of an unscarred uterus caused by adenomyosis in the early third trimester. A 33-year-old primigravid woman was referred to our department because of severe acute abdominal pain and signs and symptoms of hemorrhagic shock. Ultrasound exanimation performed at admission revealed a living, intrauterine fetus of 28 weeks gestational age with reduced amniotic fluid and presence of free peritoneal fluid. The fetal heart rate was non-reassuring with variable decelerations and severe fetal bradycardia. Emergency cesarean section revealed massive hemoperitoneum and complete rupture in the uterine fundus. Subtotal peripartum hysterectomy with conservation of adnexae was performed. Histological examination revealed adenomyosis at the site of uterine rupture.

A case of severe ADAMTS13 deficiency presenting as thrombotic thrombocytopenic purpura in pregnancy.

INTRODUCTION: Thrombotic thrombocytopenic purpura is a rare life-threatening disorder characterized by thrombocytopenia and microangiopathic hemolytic anemia. It is caused by the absent or severe deficiency of the von Willebrand Factor-cleaving protease named ADAMTS13. Pregnancy is a well recognized factor precipitating the appearance of the disease both in women that had reduced levels of ADAMTS13 activity prior to gestation and in those with other inherited or acquired thrombophilic syndromes. CASE REPORT: We report a 25-year old woman with severe ADAMTS13 deficiency presented early in her 1st pregnancy and relapsed in two subsequent gestations. This presentation is uncommon for thrombotic thrombocytopenic purpura is associated with pregnancy (ADAMTS13 deficiency < 5%, without an inhibitor). In the first pregnancy she started with daily plasma exchange 1.5 x volume, corticosteroids and IV immunoglobulin and finally entered remission after 23 sessions and termination of pregnancy. In the second pregnancy she did not receive prophylactic treatment and relapsed in the 3rd trimester. Prophylactic treatment during the third pregnancy with plasma infusions proved also ineffective to prevent relapse. DISCUSSION: Many issues regarding treatment and prevention of thrombotic thrombocytopenic purpura relapses in subsequent pregnancies are unclear. Proposed guidelines recommend that the same treatment should be performed on pregnant and non pregnant patients without modification of plasma replacement dose according to ADAMTS13 levels. In addition, many authors suggest that pregnant patients with history of thrombotic thrombocytopenic purpura and severe deficiency of ADAMTS13 levels should received prophylactic treatment for prevention of relapses in the subsequent pregnancies. CONCLUSION: Severe ADAMTS 13 deficiency may present as thrombotic thrombocytopenic purpura of pregnancy. Pregnant women with thrombotic thrombocytopenic purpura and especially with severe deficiency of ADAMTS13 levels require specific consideration regarding treatment and prophylaxis in subsequent pregnancies.

Oxidative stress due to radiation in CD34(+) hematopoietic progenitor cells: protection by IGF-1.

Radiation exerts direct as well as indirect effects on DNA through the generation of reactive oxygen species (ROS). Irradiated hematopoietic progenitor cells (HPCs) experience DNA strand breaks, favoring genetic instability, due to ROS generation. Our aim was to study the effect of a range of radiation doses in HPCs and the possible protective mechanisms activated by insulin-like growth factor-1 (IGF-1). ROS generation was evaluated, in the presence or absence of IGF-1 in liquid cultures of human HPCs-CD34(+) irradiated with 1-, 2- and 5-Gy X-rays, using a flow cytometry assay. Manganese superoxide dismutase (MnSOD) expression was studied by western blot analysis and visualized by an immunofluorescence assay. Apoptosis was estimated using the following assays: Annexin-V assay, DNA degradation assay, BCL-2/BAX mRNA and protein levels and caspase-9 protein immunofluorescence visualization. Viability and clonogenic potential were studied in irradiated HPCs. The generation of superoxide anion radicals at an early and a late time point was increased, while the hydrogen peroxide generation at a late time point was stable. IGF-1 presence further enhanced the radiation-induced increase of MnSOD at 24 h post irradiation. IGF-1 inhibited the mitochondria-mediated pathway of apoptosis by regulating the m-RNA and protein expression of BAX, BCL-2 and the BCL-2/BAX ratio and by decreasing caspase-9 protein expression. IGF-1 presence in culture media of irradiated cells restored the clonogenic capacity and the viability of HPCs as well. In conclusion, IGF-1 protects HPCs-CD34(+) from radiation effects, by eliminating the oxidative microenvironment through the enhancement of MnSOD activation and by regulating the mitochondria-mediated pathway of apoptosis.

Association of estrogen receptor alpha (ERα) gene polymorphisms with endometrial thickness and lipid profile in women with breast cancer treated with aromatase inhibitors.

Aromatase inhibitors (AIs) provide an alternative to tamoxifen as an adjuvant therapy for post-menopausal, hormone-receptor positive breast cancer patients. The aim of the present study was to evaluate the effect of PvuII and XbaI polymorphisms of the ERα gene at ΑΙs treatment's adverse effects in post-menopausal women with breast cancer. The study included 87 post-menopausal women with ER-positive breast cancer treated with AIs and 80 healthy controls. The overall presence of ERα polymorphisms in all women with breast cancer was not different from the healthy controls. Endometrial thickness under AIs treatment was reduced from (mean value ± SD) 6,404 ± 2,901 mm to 3,666 ± 1,4656 mm. Moreover, the AA XbaI genotype was associated with greater reduction in endometrial thickness during therapy with AIs (p = 0.005). The presence of the CC PvuII and the AA XbaI genotypes were associated with elevated LDL levels and elevated triglycerides. In conclusion, the results of the present study showed that the genotype of women with breast cancer under AIs treatment might influence treatment's adverse effects, as, the presence of the CC PvuII and the AA XbaI genotypes of the ERα were associated with elevated LDL and triglycerides serum levels, while the AA XbaI genotype was associated with a greater reduction in endometrial thickness.