Ceramides during Pregnancy and Obstetrical Adverse Outcomes.

Ceramides are a group of sphingolipids located in the external plasma membrane layer and act as messengers in cellular pathways such as inflammatory processes and apoptosis. Plasma ceramides are biomarkers of cardiovascular disease, type 2 diabetes mellitus, Alzheimer's disease, various autoimmune conditions and cancer. During pregnancy, ceramides play an important role as stress mediators, especially during implantation, delivery and lactation. Based on the current literature, plasma ceramides could be potential biomarkers of obstetrical adverse outcomes, although their role in metabolic pathways under such conditions remains unclear. This review aims to present current studies that examine the role of ceramides during pregnancy and obstetrical adverse outcomes, such as pre-eclampsia, gestational diabetes mellitus and other complications.

Plasma Ceramide Concentrations in Full-Term Pregnancies Complicated with Gestational Diabetes Mellitus: A Case-Control Study.

Ceramides, a sphingolipid group that acts as a messenger in cellular differentiation, proliferation, apoptosis and senescence, have been associated with cardiovascular disease and type 2 diabetes. The evidence for an association between ceramides and gestational diabetes mellitus (GDM) is scarce. This case-control study aimed to compare women with GDM with healthy, pregnant women in terms of plasma ceramide concentrations at the time of delivery. Ninety-two pregnant women were included in this case-control study, 29 in the GDM group and 63 in the control group. All women were admitted to a tertiary academic hospital for a full-term delivery. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied for the quantification of four molecular ceramides, namely Cer d18:1/16:0 (Cer16:0), Cer d18:1/18:0 (Cer18:0), Cer d18:1/24:0 (Cer24:0) and Cer d18:1/24:1 (Cer24:1) in plasma samples. The raw chromatographic data obtained from the LC-MS/MS analysis were processed using Analyst SCIEX (AB Sciex Pte. Ltd., USA). In a univariate statistical analysis, Cer24:0 concentration was significantly lower in the GDM group compared with the control group (p = 0.01). The present study demonstrated lower Cer24:0 concentrations in pregnancies complicated by GDM. Further prospective studies are required to enhance the results of this study.

Effect of Exercise on the Resting Metabolic Rate and Substrate Utilization in Women with Gestational Diabetes Mellitus: Results of a Pilot Study.

Regular physical activity during pregnancy has a positive effect on the mother and fetus. However, there is scarce data regarding the effect of exercise in pregnancies complicated by gestational diabetes mellitus (GDM). The aim of the present parallel, non-randomized, open-label, pilot, clinical study was to examine the effect of two exercise programs on the resting metabolic rate (RMR) and substrate utilization in pregnancies complicated by GDM, compared with usual care (advice for the performance of exercise). Forty-three pregnant women diagnosed with GDM between the 24th and 28th gestational week, volunteered to participate. Three groups were formed: Usual care (n = 17), Walking (n = 14), and Mixed Exercise (n = 12). The Usual care group was given advice on maintaining habitual daily activities without any additional exercise. The Walking group exercised regularly by walking, in addition to the habitual daily activities. Finally, the Mixed Exercise group participated in a program combining aerobics and strength exercises. Training intensity was monitored continuously using lightweight, wearable monitoring devices. The Walking and Mixed Exercise groups participated in the training programs after being diagnosed with GDM and maintained them until the last week of gestation. RMR and substrate utilization were analyzed using indirect calorimetry for all participants twice: between 27th and 28th gestational week and as close as possible before delivery. No differences were observed between groups regarding body composition, age, and medical or obstetrical parameters before or after the exercise programs. RMR was increased after the completion of the exercise interventions in both the Walking (p = 0.001) and the Mixed Exercise arms (p = 0.002). In contrast, substrate utilization remained indifferent. In conclusion, regular exercise of moderate intensity (either walking, or a combination of aerobic and strength training) increases RMR in women with GDM compared to the lack of systematic exercise. However, based on the present, pilot data, these exercise regimes do not appear to alter resting substrate utilization.

Humanin and diabetes mellitus: A review of in vitro and in vivo studies.

Humanin (HN) is a 24-amino acid mitochondrial-derived polypeptide with cyto-protective and anti-apoptotic effects that regulates the mitochondrial functions under stress conditions. Accumulating evidence suggests the role of HN against age-related diseases, such as Alzheimer's disease. The decline in insulin action is a metabolic feature of aging and thus, type 2 diabetes mellitus is considered an age-related disease, as well. It has been suggested that HN increases insulin sensitivity, improves the survival of pancreatic beta cells, and delays the onset of diabetes, actions that could be deployed in the treatment of diabetes. The aim of this review is to present the in vitro and in vivo studies that examined the role of HN in insulin resistance and diabetes and to discuss its newly emerging role as a therapeutic option against those conditions.

Effect of oral phytoestrogens on endometrial thickness and breast density of perimenopausal and postmenopausal women: A systematic review and meta-analysis.

BACKGROUND: Phytoestrogens constitute an alternative, non-pharmacologic approach for the management of menopausal symptoms. However, few studies have focused on their safety, specifically in relation to endometrial thickness and breast density. AIM: To systematically search for and quantitatively synthesize the evidence regarding the effect of phytoestrogens on endometrial thickness and breast density in perimenopausal and postmenopausal women. METHODS: Randomized controlled trials (RCTs) examining the effect of phytoestrogens compared with placebo or menopausal hormone therapy (MHT) on endometrial thickness and/or breast density in perimenopausal or postmenopausal women were searched for in the MEDLINE, CENTRAL and Scopus databases as well as "gray literature" sources until October 31, 2018. Main outcomes were the change from baseline in endometrial thickness and breast density. Statistical analysis was performed with RevMan 5.3, using R language and Open Meta-Analyst software. RESULTS: The meta-analysis for endometrial thickness included 30 RCTs (with a total of 3497 women), and that for breast density four RCTs (with a total of 674 women). Phytoestrogens did not affect endometrial thickness compared with placebo [weighted mean difference (WMD) -0.04 mm, 95% confidence interval (CI) -0.18 to 0.11, I2 66%] or MHT (WMD -1.40 mm, 95% CI -2.98 to 0.18, I2 84%). In addition, phytoestrogens did not affect breast density compared with placebo [standardized mean difference (SMD) -0.76, 95% CI -1.54 to 0.2, I2 95%). CONCLUSION: Phytoestrogens have no effect on endometrial thickness or breast density, when administered at various doses and for various durations, in perimenopausal and postmenopausal women. However, the high heterogeneity of the studies makes it necessary to conduct RCTs with less risk of systematic error.

Biomarkers of Endothelial Dysfunction in Women With Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of childbearing age. The criteria required for the diagnosis identify various phenotypes, with different reproductive, metabolic, and cardiovascular (CV) risk characteristics. Emerging evidence links adipocyte-secreted hormones as candidates in the pathogenesis of endothelial dysfunction in PCOS, independently of additional risk factors. The aim of this review was to collect, analyze, and qualitatively resynthesize evidence on biomarkers of endothelial dysfunction (visfatin, vascular endothelial growth factor [VEGF], matrix metalloproteinase 9 [MMP-9]) in women with PCOS. Women with PCOS exhibit (a) increased plasma visfatin concentrations compared with controls with a similar body mass index; (b) increased VEGF production along with chronic, mild inflammation; and (c) increased MMP-9 concentrations, which might be related to either excessive CV risk or abnormalities of ovarian extracellular matrix remodeling, multiple cyst formation, follicular atresia, and chronic anovulation. As PCOS has been associated with CV risk, early identification of endothelial dysfunction is clinically relevant.

Serum humanin concentrations in women with pre-eclampsia compared to women with uncomplicated pregnancies.

PURPOSE: To compare serum humanin concentrations in pregnant women with and without pre-eclampsia (PE). MATERIALS AND METHODS: A case-control study where pregnant women (PE group, n = 37; control group, n = 34) studied through history parameters (gynecological, obstetrical, personal, and family), physical and sonographic examination parameters [body mass index (BMI), blood pressure obstetrical ultrasound], and biochemical/hormonal assays [creatinine, urea, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), uric acid, platelets, urinary protein, and humanin]. RESULTS: There was no difference in basic characteristics between women with PE and control, except in parity and gravidity. Humanin concentrations were higher in women with PE compared to controls (422.2 ± 33.5 vs. 319.1 ± 28.1 pg/ml, p = 0.023). In a binary logistic analysis, humanin was associated with the presence of PE [odds ratio 1.003, 95% confidence interval (CI); 1.000-1.006]. The ability of humanin to discriminate between women with PE and controls was evaluated by receiver operation characteristics (ROC) analysis [area under the curve (AUC) 0.639, 95% CI; 0.510-0.768, p = 0.045]. CONCLUSIONS: Serum humanin concentrations are increased in women with PE, compared to women with uncomplicated pregnancies, suggesting a potential protective role of humanin against the oxidative stress and endothelial dysfunction occurring in PE.

Personal and parental acceptance of human papillomavirus vaccination prior to and during the economic crisis among women in Greece.

PURPOSE: To assess personal and parental human papillomavirus (HPV) vaccination acceptance and how it is influenced by demographic factors prior to (2005-2010) and during (2011-2016) the economic crisis in Greece. METHODS: During 2005-2016, 6,401 women aged 18-65 years, living in different areas of Greece filled in a questionnaire covering demographic characteristics, knowledge of HPV infection's natural history and its consequences and assessing their intention to receive the HPV vaccine for themselves and their children. RESULTS: Women's intention to get vaccinated before the economic crisis was higher (86.2%) than during it (82.8%). In addition, the intention of women to vaccinate their children was higher for girls during 2005-2010 (78.3%), while there was no statistically significant difference concerning boys. HPV vaccination acceptance per year showed a statistically significant variation. The initially high acceptance decreased following vaccine's release, mainly due to fear of side effects, increased following objective public education, and declined again. Demographic characteristics affected HPV vaccination acceptance at the time period before the economic crisis in Greece, but not during it. CONCLUSION: Demographic factors affecting a woman's attitude towards vaccination prior to the economic crisis in Greece, stopped playing a significant role during the crisis, reflecting its devastating effect on most parts of the population.

Regulation of basal metabolic rate in uncomplicated pregnancy and in gestational diabetes mellitus.

Basal metabolic rate (BMR) is one of the major components of total energy expenditure (TEE). It is affected by various factors, such as body weight, body composition, age, race/ethnicity, gender, biochemical parameters, physical activity, and health status. Gestational diabetes mellitus (GDM) is the most common metabolic disorder during pregnancy and it increases the risk for health complications, such as stillbirth, diabetes mellitus, and cardiovascular disease in later life. Both BMR and GDM have been linked with gestational weight gain (GWG), a fact suggesting a possible association between them. However, assessing BMR is a complex procedure, which becomes more complicated when additional parameters, such as pregnancy and GDM, are taken into consideration. The present review summarizes the current knowledge on factors affecting BMR and its regulation in relation to pregnancy and GDM. Future research addressing these associations should thoroughly consider other factors that affect BMI when designing such studies and/or discussing the BMR outcome results.

Serum visfatin, vascular endothelial growth factor and matrix metalloproteinase-9 in women with polycystic ovary syndrome.

AIM: To evaluate serum concentrations of visfatin, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in women with polycystic ovary syndrome (PCOS) and to investigate their possible role as early endothelial markers in PCOS. METHODS: Forty-two women with PCOS and 42 controls, matched for age and weight, were included in the study. Serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, total testosterone (tT), Δ4-androstenedione (Δ4A), dehydroepinadrosterone sulphate (DHEA-S), 17-OH-progesterone, sex hormone-binding protein (SHBG), thyroid-stimulating hormone (TSH), free thyroxine (fT4), visfatin, VEGF and MMP-9 were measured in all women; free androgen index (FAI) was calculated as well. Receiver-operating characteristic (ROC) analysis was performed to examine if visfatin, tT or FAI can predict the clinical status (PCOS or control). RESULTS: LH, Δ4A, tT and FAI concentrations were higher in PCOS than in controls (p = 0.002, 0.029, 0.0005 and 0.014, respectively). Visfatin, VEGF and MMP-9 concentrations were higher in women with PCOS than controls (p = 0.019, 0.001 and 0.002, respectively). In ROC analysis, area under the curve (AUC) in the prediction of clinical status was 0.641 for visfatin (p = 0.026), 0.731 for tT (p = 0.001) and 0.666 for FAI (p = 0.010), with no difference among them (p = 0.117). CONCLUSIONS: Visfatin may induce the expression of pro-angiogenic factors, such as VEGF and MMP-9, in women with PCOS, inplying gradually development of endothelial dysfunction. Further studies are required to clarify these findings.

Thyrotropin receptor autoantibodies and early miscarriages in patients with Hashimoto thyroiditis: a case-control study.

We have previously hypothesized that early miscarriage in women with Hashimoto thyroiditis might be the result of a cross-reactivity process, in which blocking autoantibodies against thyrotropin receptor (TSHr-Ab) antagonize hCG action on its receptor on the corpus luteum. To test this hypothesis from the clinical perspective, we investigated the presence of TSHr-Ab in Hashimoto thyroiditis patients with apparently unexplained, first-trimester recurrent miscarriages compared to that in Hashimoto thyroiditis patients with documented normal fertility. A total of 86 subjects (43 cases and 43 age-matched controls) were finally included in a case-control study. No difference in the prevalence of TSHr-Ab positivity was detected between cases and controls (Fisher's exact test, p value = 1.00). In patients with recurrent miscarriages, TSHr-Ab concentrations did not predict the number of miscarriages (univariate linear regression, p value = 0.08). These results were robust in sensitivity analyses, including only cases with full investigation or those with three or more miscarriages. We conclude that no role could be advocated for TSHr-Ab in the aetiology of recurrent miscarriages in women with Hashimoto thyroiditis.

Cyclosporine in the management of impetigo herpetiformis: a case report and review of the literature.

A 27-year-old female, gravida 1, para 0, in week 22 of pregnancy, presented with an eruption consisting of annular erythematosquamous plaques with an active polycyclic elevated border comprised of superficial micropustules. Clinical and histological features were typical of impetigo herpetiformis (IH). Systemic steroids resulted in an unstable condition, with no resolution of lesions. Resistance to the above therapeutic scheme served as a stimulus to discuss the use of cyclosporine as a therapeutic option in this condition. Reviewing the limited literature, cyclosporine seems to serve not as a monotherapy in the management of IH but as an additional medication, in order to achieve a stable course of the disease and avoid high doses of systemic steroids.

A therapeutic approach for female, relapsing genital lichen sclerosus: a single-center study.

OBJECTIVE: To assess the efficacy of methylprednisolone aceponate 0.1% (MPA 0.1%) in female genital lichen sclerosus (GLS) and efficacy of MPA, tacrolimus or emollient for prevention of flares. METHODS: A single-center, retrospective study was conducted. At baseline, female patients with relapsing GLS (n = 46) were treated with MPA 0.1% applied once daily for 8 weeks. Visual Analog Scale (VAS) score for vulvar pruritus and Investigator's Global Assessment (IGA) score were recorded at baseline, weeks 8 and 20. At week 8, patients responsive to treatment (n = 38) were further treated with MPA 0.1% twice weekly (n = 15), tacrolimus once daily (n = 13) or topical emollient once daily (n = 10), as maintenance therapy until week 20. RESULT: Both VAS and IGA median score was significantly decreased from baseline to week 8 (p = 0.000). At week 20, both median VAS and IGA scores differed significantly between patients treated with emollient and patients treated with MPA 0.1% (p = 0.000) and patients treated with emollient and patients treated with tacrolimus (p = 0.000); patients treated with MPA 0.1% presented no significant difference in either median VAS score (p = 0.032) or median IGA score (p = 0.636) at week 20 compared to patients treated with tacrolimus. CONCLUSIONS: MPA 0.1% is effective in relapsing female GLS. MPA 0.1% and tacrolimus have equal efficacy in preventing relapses.

Hormone therapy and asymmetrical dimethylarginine in postmenopausal women.

Women present an estradiol-dependent cardiovascular risk profile. Based on various studies, it was considered that estrogen therapy (ET) in postmenopausal women could probably reduce the higher cardiovascular risk in this group. Assymetric dimethylarginine (ADMA) is an endogenous methylated arginine which inhibits nitric oxide (NO) synthesis by competing with the substrate of NO, L-arginine, leading to endothelial dysfunction and, consequently, to atherosclerosis. Moreover, ADMA has been considered as an independent risk factor for cardiovascular disease. It has also been found that hormone therapy (HT), and mainly oral estrogen therapy, lowers ADMA concentrations in healthy postmenopausal women. The effect of estrogens on ADMA levels, although small, is considered important, as physiological variation of ADMA is limited. Nevertheless, larger randomized trials are necessary to establish that estrogens substantially lower ADMA levels and that these changes really reflect improved cardiovascular prognosis in postmenopausal women.

Maternal physical activity before and during early pregnancy as a risk factor for gestational diabetes mellitus.

The aim of this study was to assess whether the levels of physical activity before and during early pregnancy are associated with the prevalence of gestational diabetes mellitus (GDM). The study group included 160 puerperas. Among them, 40 (25%) diagnosed as having GDM during their recent pregnancy, whereas the remaining 120 (75%) served as controls. The international physical activity questionnaire (IPAQ-Greek version) was applied twice, in an attempt to estimate the level of physical activity before and during early pregnancy. Women who were "inactive" before or during early pregnancy had odds ratio (OR) 7.9 [95% confidence interval (CI) 3.7-16.56] and 1.3 (95% CI 1.2-1.4) of developing GDM, compared to "minimally active" or "active" women, respectively. Pregnancy resulted in a decrease in the level of physical activity (P < 0.005) during early pregnancy, independently of the diagnosis of GDM and morbidity during early pregnancy. We conclude that physical inactivity before and during early pregnancy is associated with increased risk for developing GDM in late pregnancy.

The impact on ovarian reserve after laparoscopic ovarian cystectomy versus three-stage management in patients with endometriomas: a prospective randomized study.

OBJECTIVE: To investigate the effect of two different laparoscopic methods on ovarian reserve in patients with ovarian endometriomas. DESIGN: Prospective, randomized clinical trial. SETTING: Endoscopy unit of a university hospital. PATIENT(S): Twenty women with endometriomas. INTERVENTION(S): Patients were randomly selected to undergo either laparoscopic cystectomy for endometrioma (group 1) or the "three-step procedure" (group 2). Before and 6 months after laparoscopy all patients were evaluated, and 12 months postoperatively they underwent ultrasound scan examination. MAIN OUTCOME MEASURE(S): The primary end point was ovarian reserve damage based on the alterations of anti-Müllerian hormone (AMH). Secondary end points were the changes of antral follicle count and serum concentration of FSH, LH, E(2), and inhibin B. RESULT(S): Mean serum AMH was reduced significantly from 3.9-2.9 ng/mL in group 1 compared with the reduction from 4.5-3.99 ng/mL in group 2. CONCLUSION(S): Ovarian reserve determined by AMH is less diminished after the three-step procedure compared with cystectomy of endometriomas.

Complete uterine inversion during caesarean section: A case report.

Inversion of the uterus through the uterine lower segment incision during a caesarean section is an extremely rare obstetric incident. It consists, though, an emergency complication that is potentially life-threatening, especially in cases of prolonged inversion, because haemodynamic instability and shock may occur. Prompt diagnosis and immediate uterine reversion are the key actions in the management of this serious complication.