Recent advances in prophylactics and treatment of osteoporosis.

Recently, a dramatic increase in the average life expectancy has been noted, regarded as the one of the greatest achievements of the last decades, but in consequence osteoporosis affects millions of people all over the world. Currently osteoporosis is defined as a skeletal disorder characterized by compromised bone strength which leads to an increased risk of fractures. The most commonly used tool to evaluate the 10-year risk of fractures is the fracture risk assessment tool validated in many independent cohorts. Osteoporosis itself has no symptoms, but fractures are common symptoms of osteoporosis which can result in disability and mortality. Hence, osteoporosis is called a silent epidemic as well as a silent killer. The best way to assess patients with osteoporosis is by using the most widely employed techniques - dual-energy X-ray absorptiometry or quantitative computed tomography. There are a lot of precisely documented risk factors of osteoporosis - e.g. cigarette smoking, alcohol use, getting little or no exercise, being small-framed or thin, a diet low in foods containing calcium and vitamin D - and their limitation or elimination is the best way for prophylactics of this dangerous disease. Some other risk factors such as age and sex of patients should not be omitted in the decision making process. In the literature there are numerous therapeutic proposals and different guidelines. In this review we present the recent advances in the prophylactics and treatment of osteoporosis.

Disturbances of modulating molecules (FOXP3, CTLA-4/CD28/B7, and CD40/CD40L) mRNA expressions in the orbital tissue from patients with severe graves' ophthalmopathy.

Purpose. To evaluate the relationship between the expression of orbital tissue mRNA for FOXP3, CTLA-4/CD28/CD80/CD86, and CD40/CD40 and the severity of Graves' orbitopathy (GO). Material and Methods. Orbital tissue was obtained from 26 patients with GO, with mild (n = 6) or severe GO (n = 20), and 7 healthy controls. The expression of mRNA of FOXP3, CTLA-4/CD28/CD80/CD86, CD40/CD40L was measured by RT-PCR. TCR and CD3 were evaluated by immunohistochemistry. Results. Higher mRNA for FoxP3 (relative expression: 1.4) and CD40 (1.27) and lower expression of CTLA-4 (0.61) were found in the GO tissues versus controls. In severe GO as compared to mild GO higher mRNA expression for FoxP3 (1.35) and CD40 (1.4) and lower expression for CTLA-4 (0.78), CD28 (0.62), and CD40L (0.56) were found. A positive correlation was found between FOXP3 mRNA and CD3 infiltration (R = 0.796, P = 0.0000001). Conclusions. The enhanced FOXP3 mRNA expression in GO samples may suggest the dysfunction of FOXP3 cells in the severe GO. The diminished mRNA expression of CTLA-4 in severe GO may indicate inadequate T regulatory function. The enhanced mRNA expression of CD40 in severe GO and negative correlation to CRP mRNA may suggest their role in the active and inactive GO.

Seroprevalence of parvovirus B19 antibodies among young pregnant women or planning pregnancy, tested for toxoplasmosis.

INTRODUCTION AND OBJECTIVE: Acute parvovirus B19 (B19V) infection is a proven risk for pregnant women and fetus. The aim of this study was to determine the prevalence of B19V antibodies among pregnant women or planning pregnancy, who were referred for preventive toxoplasmosis screening. MATERIAL AND METHODS: Between 2007-2010, 55 women in the age between 21 and 40 years were tested for both B19V IgG and IgM antibodies and sociodemographic information was collected. RESULTS: Among the study group, the mean age was 30 years, 43.6% of women were positive only for B19V IgG antibodies, 9% were positive for both B19V IgG and IgM antibodies and 11% were positive only for B19V IgM antibodies. Women negative for B19 IgG antibodies (47.3%) were considered as a high-risk group of B19V viremia. The serological profile indicating infection with Toxoplasma gondii was considered as a risk factor for fetal distress. The T. gondii IgG antibodies were detected in 51% cases, in 32.7% antibodies were positive for both IgG and IgM, while in 16.3% cases both IgG and IgM were negative. CONCLUSIONS: B19V infection and overlapping of other independent risk factors during pregnancy pose a significant hazard to fetus during development. Therefore, we recommend further broadening the epidemiological database of B19V infection prevalence among women. B19V infection should be taken into account during differential diagnosis as a cause of miscarriage.

Serum irisin concentration in women with gestational diabetes.

Irisin is a novel myokine and adipokine which induces an increase in total body energy expenditure, improving insulin sensitivity and glucose tolerance in experimental animals. In the present study, serum irisin concentration was measured by an enzyme immunoassay in 130 women with gestational diabetes mellitus (GDM) and 140 BMI-matched patients with normal glucose tolerance (NGT). Median irisin level was significantly lower in the patients with GDM than in the NGT subjects (1703.3 [1354.8-2097.9 ng/ml] versus 1873.8 [1519.8-2294.8 ng/ml], p = 0.01); however, 3 months after childbirth its concentrations did not differ markedly between the two groups (1165.9 [872.1-1497.5] ng/ml versus 1139.0 [984.0-1376.7] ng/ml). In the whole group, irisin concentration correlated negatively with 2 h glucose level (R = -0.14, p = 0.03). In the women with NGT, irisin concentration correlated positively with IS(OGTT) (R = 0.22, p = 0.04) and the disposition index (DI(120)) (R = 0.24, p = 0.03), as well as negatively with 2 h insulin level (R = -0.23, p = 0.03) and HOMA-IR (R = -0.24, p = 0.02). Multiple regression analysis revealed that 2 h glucose and DI(120) were the only variables significantly influencing serum irisin (ß = 0.158, p = 0.03 and ß = 0.159, p = 0.02, respectively). Our results suggest that serum irisin concentration increases markedly in pregnant women, but this increase seems to be significantly lower in patients with GDM.

[The role of inositol deficiency in the etiology of polycystic ovary syndrome disorders]. / Rola niedoboru inozytolu w patofizjologii zaburzen wystepujacych w zespole policystycznych jajników.

Inositol acts as a second messenger in insulin signaling pathway Literature data suggest inositol deficiency in insulin-resistant women with the polycystic ovary syndrome. Supplementation of myo-inisitol decreases insulin resistance as it works as an insulin sensitizing agent. The positive role of myo-inositol in the treatment of polycystic ovary syndrome has been of increased evidence recently The present review presents the effects of myo-inositol on the ovarian, hormonal and metabolic parameters in women with PCOS.

MicroRNAs expression profiling of eutopic proliferative endometrium in women with ovarian endometriosis.

BACKGROUND: The eutopic endometrium of women with endometriosis, compared with disease-free individuals, contains certain molecular alterations, including the differential expression of microRNA (miRNA). The aim of the study was to compare the expression of the most relevant miRNAs in the eutopic endometrium of women with and without ovarian endometriosis. METHODS: A total of 46 regularly menstruating patients, 21 patients with ovarian endometriosis and 25 controls, underwent surgery in the proliferative phase of the cycle. The eutopic endometrium was collected through aspirating biopsy prior to laparoscopy. Only patients with advanced (stage III and IV) histopathologically confirmed ovarian endometriosis were included. TaqMan MicroRNA Array Cards were applied to examine the expression of 667 human miRNAs in 10 patients with endometriosis and 10 controls. Custom-made, low-density real-time PCR arrays were used to confirm the expression of 15 selected molecules in 21 endometriosis patients and 25 disease-free individuals. RESULTS: Of 667 miRNAs, 2 were highly likely to be upregulated and 13 were downregulated in the eutopic endometrium of patients with endometriosis compared with the controls. Validation using real-time PCR showed that hsa-miR-483-5p (p = 0.012) and hsa-miR-629* (p = 0.02) are significantly downregulated in patients with endometriosis. CONCLUSIONS: Changes in the expression of select miRNAs might lead to or be a consequence of an early defect in the physiological activity of the proliferative endometrium, ultimately resulting in the overgrowth of this tissue outside the uterus.

Implantation of embryos. The way for the improvement of the cumulative life birth rate (CLBR) in the assisted reproductive technology (ART).

Despite the willingness, humans belong to the species with the limited procreation possibilities. Infertility affects about 15% of population is the very important subject for the reproductive medicine. An assisted reproductive technology (ART) offers the significant chance for the infertile couples, but it does not give the guarantee for the pregnancy and for the birth of a healthy child. The implantation of embryo, despite numerous trials and attempts, remain the last barrier in the assisted reproduction technologies; thus, the endometrial receptivity becomes the subject of permanent interest. In this review we have tried to present various methods of improvement of an endometrial receptivity with the conclusion that we still wait for the valuable prognostic factor in the treatment of infertility by ART which could predict the chance for the birth of a healthy child.

Identification of serum miR-1246 and miR-150-5p as novel diagnostic biomarkers for high-grade serous ovarian cancer.

Epithelial ovarian cancer (EOC) is one of the leading cancers in women, with high-grade serous ovarian cancer (HGSOC) being the most common and lethal subtype of this disease. A vast majority of HGSOC are diagnosed at the late stage of the disease when the treatment and total recovery chances are low. Thus, there is an urgent need for novel, more sensitive and specific methods for early and routine HGSOC clinical diagnosis. In this study, we performed miRNA expression profiling using the NanoString miRNA assay in 34 serum samples from patients with HGSOC and 36 healthy women. We identified 13 miRNAs that were differentially expressed (DE). For additional exploration of expression patterns correlated with HGSOC, we performed weighted gene co-expression network analysis (WGCNA). As a result, we showed that the module most correlated with tumour size, nodule and metastasis contained 8 DE miRNAs. The panel including miR-1246 and miR-150-5p was identified as a signature that could discriminate HGSOC patients with AUCs of 0.98 and 1 for the training and test sets, respectively. Furthermore, the above two-miRNA panel had an AUC = 0.946 in the verification cohorts of RT-qPCR data and an AUC = 0.895 using external data from the GEO public database. Thus, the model we developed has the potential to markedly improve the diagnosis of ovarian cancer.

The expression of suppressor of cytokine signaling 1 and 3 in fat and placental tissue from women with gestational diabetes.

The suppressor of cytokine signaling (SOCS) proteins are feedback inhibitors of signaling pathways induced by cytokines, hormones and growth factors. In the present study we measured the expression of SOCS1, SOCS3, interleukin-6 (IL-6), IL-6 receptor, IL-8 and leptin mRNA in paired samples of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and placental tissue obtained from 18 pregnant women with normal glucose tolerance (NGT) and 20 subjects with gestational diabetes mellitus (GDM), using quantitative RT-PCR. The patients with GDM had significantly higher IL-8 mRNA expression in VAT than the women with NGT (p = 0.007), whereas the expression of SOCS1, SOCS3 and other genes study did not differ significantly between the two groups. Stepwise regression analysis revealed that SOCS1 mRNA expression in VAT was significantly associated with prepregnancy BMI (ß = -0.68, p = 0.03) and IL-8 mRNA expression (ß = 0.66, p = 0.03), whereas SOCS3 mRNA expression in VAT was independently predicted by IL-6 mRNA expression (ß = 0.94, p = 0.0002, R(2) = 0.88). In conclusion, our results did not show significant differences in SOCS1 and SOCS3 mRNA expression in adipose and placental tissue obtained from pregnant women with and without GDM.

Serum C18:1-Cer as a Potential Biomarker for Early Detection of Gestational Diabetes.

We hypothesized that sphingolipids may be early biomarkers of gestational diabetes mellitus (GDM). Here, 520 women with normal fasting plasma glucose levels were recruited in the first trimester and tested with a 75 g oral glucose tolerance test in the 24th-28th week of pregnancy. Serum sphingolipids concentrations were measured in the first and the second trimester by ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC/MS/MS) in 53 patients who were diagnosed with GDM, as well as 82 pregnant women with normal glucose tolerance (NGT) and 32 non-pregnant women. In the first trimester, pregnant women showed higher concentrations of C16:0, C18:1, C22:0, C24:1, and C24:0-Cer and lower levels of sphinganine (SPA) and sphingosine-1-phosphate (S1P) compared to non-pregnant women. During pregnancy, we observed significant changes in C16:0, C18:0, C18:1, and C24:1-Cer levels in the GDM group and C18:1 and C24:0-Cer in NGT. The GDM (pre-conversion) and NGT groups in the first trimester differed solely in the levels of C18:1-Cer (AUC = 0.702 p = 0.008), also considering glycemia. Thus, C18:1-Cer revealed its potential as a GDM biomarker. Sphingolipids are known to be a modulator of insulin resistance, and our results indicate that ceramide measurements in early pregnancy may help with GDM screening.

miRNAs as Predictive Factors in Early Diagnosis of Gestational Diabetes Mellitus.

Introduction: Circulating miRNAs are important mediators in epigenetic changes. These non-coding molecules regulate post-transcriptional gene expression by binding to mRNA. As a result, they influence the development of many diseases, such as gestational diabetes mellitus (GDM). Therefore, this study investigates the changes in the miRNA profile in GDM patients before hyperglycemia appears. Materials and Methods: The study group consisted of 24 patients with GDM, and the control group was 24 normoglycemic pregnant women who were matched for body mass index (BMI), age, and gestational age. GDM was diagnosed with an oral glucose tolerance test between the 24th and 26th weeks of pregnancy. The study had a prospective design, and serum for analysis was obtained in the first trimester of pregnancy. Circulating miRNAs were measured using the NanoString quantitative assay platform. Validation with real time-polymerase chain reaction (RT-PCR) was performed on the same group of patients. Mann-Whitney U-test and Spearman correlation were done to assess the significance of the results. Results: Among the 800 miRNAs, 221 miRNAs were not detected, and 439 were close to background noise. The remaining miRNAs were carefully investigated for their average counts, fold changes, p-values, and false discovery rate (FDR) scores. We selected four miRNAs for further validation: miR-16-5p, miR-142-3p, miR-144-3p, and miR-320e, which showed the most prominent changes between the studied groups. The validation showed up-regulation of miR-16-5p (p<0.0001), miR-142-3p (p=0.001), and miR-144-3p (p=0.003). Conclusion: We present changes in miRNA profile in the serum of GDM women, which may indicate significance in the pathophysiology of GDM. These findings emphasize the role of miRNAs as a predictive factor that could potentially be useful in early diagnosis.

Retinol-binding protein 4 in adipose and placental tissue of women with gestational diabetes.

In the present study, we evaluated serum levels of retinol-binding protein 4 (RBP4) and the expression of RBP4, glucose transporter-4 (GLUT4) and peroxisome proliferator activated receptor gamma (PPARγ) mRNA (using quantitative real time-PCR) in subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and placental tissue obtained from patients with gestational diabetes (GDM) and healthy pregnant women. Serum RBP4 concentrations and its expression in SAT were higher in the women with GDM than in the controls (p = 0.03). No association between serum or tissue RBP4 and the indices of insulin resistance was noted. In the GDM group serum RBP4 correlated with its mRNA expression in SAT (r = 0.67, p = 0.007). Stepwise regression analysis revealed that RBP4 mRNA expression in SAT was independently predicted by GLUT4 mRNA expression (ß= 0.59, p = 0.003) and the presence of GDM (ß=0.46, p = 0.01), whereas RBP4 mRNA expression in VAT was related to PPARγ mRNA expression (ß= 0.64, p = 0.0003) and the patient's age (ß= -0.38, p = 0.03). In conclusion, our results suggest that the elevated expression of RBP4 in SAT may contribute to the increase in circulating RBP4 in GDM subjects.

Ceramides and Sphingosino-1-Phosphate in Obesity.

Obesity is a growing worldwide problem, especially in developed countries. This disease adversely affects the quality of life and notably contributes to the development of type 2 diabetes, metabolic syndrome, and cardiovascular disorders. It is characterised by excessive lipids accumulation in the subcutaneous and visceral adipose tissue. Considering the secretory function of adipose tissue, this leads to impaired adipokines and cytokines release. Changes in adipose tissue metabolism result in chronic inflammation, pancreatic islets dysfunction and peripheral insulin resistance. In addition to saturating various adipocytes, excess lipids are deposited into non-adipose peripheral tissues, which disturbs cell metabolism and causes a harmful effect known as lipotoxicity. Fatty acids are metabolised into bioactive lipids such as ceramides, from which sphingolipids are formed. Ceramides and sphingosine-1-phosphate (S1P) are involved in intracellular signalling, cell proliferation, migration, and apoptosis. Studies demonstrate that bioactive lipids have a crucial role in regulating insulin signalling pathways, glucose homeostasis and ß cell death. Data suggests that ceramides may have an opposite cellular effect than S1P; however, the role of S1P remains controversial. This review summarises the available data on ceramide and sphingolipid metabolism and their role in obesity.

Proven and unproven methods for diagnosis and treatment of infertility.

Infertility and subfertility affect a significant part of the population. Among various definitions of this pathology, the most common one is provided by the World Health Organisation; it says that infertility is 'a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourses'. The global prevalence of infertility is about 50-70 million couples. Since the process of human reproduction involves a large number of factors, a broad spectrum of infertility tests might be applied. Some of the tests focus directly on the pregnancy, some are only partially effective, whereas others should not be recommended for infertile couples. The aim of this review is to present a critical evaluation of the infertility diagnostic process and to discuss the recommendations for its most effective treatment.

High resistin and interleukin-6 levels are associated with gestational diabetes mellitus.

Resistin is a cysteine-rich adipokine originally described as a molecular link between obesity and insulin resistance in rodents. In this study, we hypothesised that serum resistin concentrations are elevated in patients with gestational diabetes mellitus (GDM) when compared with pregnant women with normal glucose tolerance (NGT) and related to proinflammatory interleukin-6 (IL-6) and other factors conferring insulin resistance. Serum resistin and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA) in 81 women with GDM, 82 women with NGT between 24 and 31 weeks of gestation and 25 healthy non-pregnant women. Resistin concentrations were significantly higher in the GDM (21.9 [17.55-25.40] ng/ml) than in the NGT group (19.03 [15.92-23.91] ng/ml, p = 0.047), as well as in the non-pregnant women (14.8 [13.7-16.6] ng/ml, p < 0.0001). Serum IL-6 levels were elevated in the GDM (1.0 [0.7-1.5] pg/ml) as compared with the NGT group (0.8 [0.5-1.1] pg/ml, p = 0.006) and the non-pregnant controls (0.7 [0.5-1.1] pg/ml, p = 0.04). Multiple regression analysis revealed that in the pregnant women circulating resistin was related to serum IL-6 (beta = 0.33, p = 0.0004) but not to insulin or the index of insulin resistance. It is concluded that the finding of high resistin and IL-6 levels in women with gestational diabetes might confirm a role of low-grade inflammation in the pathogenesis of GDM.

[Prognosis of the IVF ICSI/ET procedure efficiency with the use of artificial neural networks among patients of the Department of Reproduction and Gynecological Endocrinology]. / Prognozowanie skutecznosci procedury IVF ICSI/ET--wsród pacjentek Kliniki Rozrodczosci i endokrynologii ginekologicznej--z wykorzystaniem sieci neuronowych.

OBJECTIVES: Prognosis of pregnancy for patients treated with IVF ICSI/ET methods, using artificial neural networks. MATERIAL AND METHODS: Retrospective study of 1007 cycles of infertility treatment of 899 patients of Department of Reproduction and Gynecological Endocrinology in Bialystok. The subjects were treated with IVF ICSI/ET method from August 2005 to September 2008. RESULTS: Classifying artificial neural network is described in the paper Architecture of the network is three-layered perceptron consisting of 45 neurons in the input layer 14 neurons in the hidden layer and a single output neuron. The source data for the network are 36 variables. 24 of them are nominal variables and the rest are quantitative variables. Among non-pregnancy cases only 59 prognosis of the network were incorrect. The results of treatment were correctly forecast in 68.5% of cases. The pregnancy was accurately confirmed in 49.1% of cases and lack of pregnancy in 86.5% of cases. CONCLUSIONS: Treatment of infertility with the use of in vitro fertilization methods continues to have too low efficiency per one treatment cycle. To improve this indicator it is necessary to find dependencies, which describe the model of IVF treatment. The application of advanced methods of bioinformatics allows to predict the result of the treatment more effectively With the help of artificial neural networks, we are able to forecast the failure of the treatment using IFV ICSI/ET procedure with almost 90% probability of certainty These possibilities can be used to predict negative cases.

Serum visfatin concentration is elevated in pregnant women irrespectively of the presence of gestational diabetes.

OBJECTIVES: The aim of the present study was to compare serum concentrations of a recently identified namely--visfatin between pregnant women with normal glucose tolerance (NGT) and gestational diabetes mellitus (GDM), as well as non-pregnant healthy subjects. MATERIALS AND METHODS: Serum visfatin concentration was measured in 61 patients with GDM, 63 pregnant subjects with NGT and 36 non-pregnant healthy women by means of an immunoassay. RESULTS: Median visfatin levels did not differ in the women with GDM (14.8 [10.8-17.3] microg/l) and NGT (15.3 [11.8-19.4] microg/l), but were significantly higher than those found in the non-pregnant women (11.4 [8.6-15.2] microg/l, p=0.0008 vs NGT and p=0.008 vs GDM group). Visfatin concentrations correlated significantly with fasting insulin (R=0.20, p=0.01), HOMA-IR (R=0.19, p=0.02) and HOMA-%B (R=0.23, p=0.004). Stepwise regression analysis revealed that serum visfatin levels were significantly predicted only by HbA1c values (b=0.21, p=0.04). CONCLUSIONS: Serum visfatin concentrations are elevated in pregnant women, irrespectively of their glucose tolerance status. This elevation may be caused by an additional secretion of visfatin from the placenta, however other possible sources of visfatin should also be taken into account.

Myoinositol in the Prevention of Gestational Diabetes Mellitus: Is It Sensible?

Gestational diabetes mellitus (GDM) is a complication that increasingly affects pregnant women. Due to the risk of adverse outcomes in the mother as well as in the fetus which is caused by GDM, appropriate diagnosis and treatment is very essential. Nevertheless, it is important to find new, effective ways of prevention of GDM to avoid side effects. A promising example of such an action may be supplementation of myoinositol. As shown in studies, myoinositol may reduce the risk of developing gestational diabetes mellitus by improving insulin sensitivity.

A comparison of the International Association of Diabetes and Pregnancy Study Groups Recommendations with Former Criteria for Diagnosing Gestational Diabetes Mellitus: A Retrospective Cohort Study.

AIM: The aim of the study was to compare the frequency of gestational diabetes mellitus (GDM) and pregnancy outcomes in women diagnosed by WHO 1999 and IADPSG criteria. METHODS: This was a retrospective cohort study comprising 1508 women who underwent a 75-g OGTT after the 24th week of gestation at the University Hospital of Bialystok between 2004 and 2012. RESULTS: GDM was diagnosed by WHO 1999 criteria in 486 (32.2%) patients and by IADPSG criteria in 397 (26.3%) women. Three hundred fifty five (23.5%) patients fulfilled both criteria, whereas 111 (7.4%) and 39 (2.6%) subjects met only WHO 1999 or IADPSG criteria, respectively. Isolated fasting hyperglycemia was found in 3.4% of patients fulfilling WHO 1999 criteria and in 17.6% of women who met IADPSG criteria. In total, fasting glycemic value was diagnostic in 42.8% of the participants fulfilling the new criteria. The main risk factor for GDM was family history of diabetes (OR 2.285 [95%CI: 1.772-2.945], p=0.00001). The rates of cesarean section and macrosomia were higher in the group with GDM than in the healthy women (54.7% vs 41.9% and 18.9% vs 13.9%, respectively), but the differences were not significant. Three months postpartum the disturbances of glucose tolerance were found in 21% of the patients with GDM. CONCLUSIONS: The introduction of the IADPS criteria did not increase the prevalence of GDM, but increased the number of patients with fasting hyperglycemia. Twelve weeks postpartum the patients with prior GDM had significantly higher post-load glucose levels than the healthy women.