Potentialization of N-a-tosyl-L-phenylalanine chloromethyl ketone (TPCK) cytotoxic activity by 2-(1-adamantylamino)-6-methylpyridine (AdAMP) in human ovarian cancer cells

Objectives: TNF is one of the key cytokines involved in cancer development. TNF signaling can result in both stimulating and inhibitory signals that can result in opposite biological effects in cancerogenesis. 2-(1-adamantylamino)-6-methylpyridine (AdAMP) enhances TNF secretion whereas N-a-tosyl-L-phenylalanine chloromethyl ketone (TPCK) is a NF-κB inhibitor potentially stimulating proapoptotic TNF signals. The aim of the study was to assess the effect of TPCK in combination with AdAMP on human ovarian cells. Material and methods: CAOV-1 human ovarian cell line was incubated with TPCK and AdAMP for 24 hours. The cytotoxic effect was evaluated in a crystal violet assay. A monoclonal antibody against TNF, Infliximab, was added to examine the possible mechanism of interactions. Results: Depending on concentration, AdAMP potentialized cytotoxic activity of TPCK or had a synergistic effect with TPCK. Infliximab did not reverse cytotoxicity of AdAMP and TPCK and in some cytotoxic and non-cytotoxic concentrations even enhanced their cytotoxicity. Conclusions: AdAMP and TPCK cytotoxicity seems to be dependent on TNF signaling, however, the exact mechanism of interactions remains unclear

Endometrial microbiota — do they mean more than we have expected?

Low biomass microbiome has an increasing importance in today’s fertility studies. There are more and more indicationsfor incorporating upper gynecological tract microbiome content in patients diagnostic and in vitro fertilization process, asdoing so may help to evaluate chances for a positive outcome. An abnormal endometrial microbiota has been associatedwith implantation failure, pregnancy loss, and other gynecological and obstetrical conditions. Furthermore it has beenshown, that using molecular methods in addition to routine diagnostics may help diagnose chronic endometritis or evenindicate cancerogenic changes. Understanding the significance of microbiome in endometrium may completely changetherapeutic approach in treatment of this part of reproductive tract. Next generation sequencing (NGS) has allowed toisolate culturable and unculturable bacteria from female reproductive tract and is a cheaper and quicker alternative forother widely known and used methods

Prognostic value of tissue plasminogen activator (tPA) in patients with epithelial ovarian cancer undergoing chemotherapy

Objectives: Tissue plasminogen activator (tPA) is a key enzyme for fibrin degradation and the proteolytic defense against formation of the thrombotic endothelial deposits. tPA is involved in carcinogenesis but its exact role in tumor biology is not very well understood and a prognostic value of tPA remains ambiguous in different cancers. The aim of the study was to assess the prognostic value of plasma tPA in patients with epithelial ovarian cancer (EOC) in the course of the first line chemotherapy.  Material and methods: the study covered 60 patients with EOC who underwent the 1st line chemotherapy. Plasma tPA was assessed at onset, after 3 and 6 cycles of chemotherapy. The groups were stratified according to tPA level at onset of chemotherapy (low tPA group < 6.5 mg/L, N = 37 and high tPA group > 6.5 mg/L, N = 23). Survival analysis was repeated for the cut-off of tPA level at 6.5 mg/L and 5.1 mg/L after 3 and 6 cycles.  Results: Only subjects with tPA > 6.5 mg/L at onset of chemotherapy had a significantly lower probability of a 5-year survival (34.8% vs. 72.7%, P < 0.006) and lower chance for disease free survival within 5 years (39.3% vs. 72.7%, P < 0.014). tPA < 6.5 mg/L plasma level evaluated at onset of chemotherapy was an independent marker of better overall survival (RR = 0.44, 95%CI = 0.19–0.98) but not disease-free survival.  Conclusions: Plasma tPA may serve as a marker of survival if assessed at onset of the first line chemotherapy in patients with ovarian cancer.

Insulin resistance indexes in women with premature ovarian insufficiency — a pilot study

  Objectives: Premature ovarian insufficiency (POI) is associated with hypoestrogenism and an increased risk of metabolic disorders. In many clinics, a variety of insulin resistance (IR) tests are used during routine clinical assessments. To date, there is no clear opinion about which of these tests should be applied in women with premature ovarian insufficiency (POI). Therefore, our preliminarily aim was to compare the most frequently used insulin resistance indexes in the clinical assessment of a group of POI women and a control group. Material and methods: Our retrospective study included 98 women with karyotypically normal spontaneous POI aged 18–39 years and a control group of 78 healthy women. Each patient was given an oral glucose tolerance test (OGTT) to evaluate their insulin release and insulin resistance. In addition, each woman’s insulin resistance (IR) was evaluated us­ing the homeostasis model assessment for insulin resistance (HOMA-IR), the quantitative insulin sensitivity check index (QUICKI), the fasting glucose-to-insulin ratio (FGIR), and Matsuda and McAuley indexes. The two groups’ glucose levels were compared at 0, 60 and 120 min of the OGTT. Results: At 0 and 60 min of the OGTT, the insulin levels of the POI women were significantly higher than those of the control group. The number of women in whom IR was detected using the various kits was comparable between the two groups. Conlusions: In conclusion, only the OGTT evaluation revealed a significant difference in insulin concentrations between the two study groups. The indexes most commonly used to detect IR did not detect differences in IR between the POI women and the members of the healthy control group. QUICKI detected significantly more women with IR within both study groups than other tests did

How to deal with hyperprolactinaemia?

Abstract Hyperolactinaemia is the most common endocrine disorder of the hypothalamic -pituitary axis. Normal range of assay is 1-25 ng/ml. Physiologically production of prolactin increased during stress, breast feeding, exercise and sleep. Hyperprolactinaemia is defined as a prolactin (PRL) level exceeding 25 ng/ml

Exome sequencing to explore the possibility of predicting genetic susceptibility to the joint occurrence of polycystic ovary syndrome and Hashimoto’s thyroiditis

A large body of evidence indicates that women with polycystic ovary syndrome (PCOS) have a higher risk of developing Hashimoto’s thyroiditis (HT) than healthy individuals. Given the strong genetic impact on both diseases, common predisposing genetic factors are possibly involved but are not fully understood. Here, we performed whole-exome sequencing (WES) for 250 women with sporadic PCOS, HT, combined PCOS and HT (PCOS+HT), and healthy controls to explore the genetic background of the joint occurrence of PCOS and HT. Based on relevant comparative analyses, multivariate logistic regression prediction modeling, and the most informative feature selection using the Monte Carlo feature selection and interdependency discovery algorithm, 77 variants were selected for further validation by TaqMan genotyping in a group of 533 patients. In the allele frequency test, variants in RAB6A, GBP3, and FNDC7 genes were found to significantly (padjusted < 0.05) differentiated the PCOS+HT and PCOS groups, variant in HIF3A differentiated the PCOS+HT and HT groups, whereas variants in CDK20 and CCDC71 differentiated the PCOS+HT and both single disorder groups. TaqMan genotyping data were used to create final prediction models, which differentiated between PCOS+HT and PCOS or HT with a prediction accuracy of AUC = 0.78. Using a 70% cutoff of the prediction score improved the model parameters, increasing the AUC value to 0.87. In summary, we demonstrated the polygenic burden of both PCOS and HT, and many common and intersecting signaling pathways and biological processes whose disorders mutually predispose patients to the development of both diseases

Anti-Müllerian Hormone in Pathogenesis, Diagnostic and Treatment of PCOS

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-aged women. It is characterized by chronic anovulation, hyperandrogenism, and the presence of polycystic ovary in ultrasound examination. PCOS is specified by an increased number of follicles at all growing stages, mainly seen in the preantral and small antral follicles and an increased serum level of Anti-Müllerian Hormone (AMH). Because of the strong correlation between circulating AMH levels and antral follicle count on ultrasound, Anti-Müllerian Hormone has been proposed as an alternative marker of ovulatory dysfunction in PCOS. However, the results from the current literature are not homogeneous, and the specific threshold of AMH in PCOS and PCOM is, therefore, very challenging. This review aims to update the current knowledge about AMH, the pathophysiology of AMH in the pathogenesis of PCOS, and the role of Anti-Müllerian Hormone in the treatment of this syndrome

The Impact of Selected Bacterial Sexually Transmitted Diseases on Pregnancy and Female Fertility

Sexually transmitted infections (STIs) caused by Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium are a common cause of pelvic inflammatory disease (PID) which can lead to tubal factor infertility (TFI). TFI is one of the most common causes of infertility, accounting for 30% of female fertility problems. STIs can also have an impact on pregnancy, leading to adverse pregnancy outcomes. Escalating antibiotic resistance in Neisseria gonorrhoeae and Mycoplasma genitalium represents a significant problem and can be therapeutically challenging. We present a comprehensive review of the current treatment options, as well as the molecular approach to this subject. We have given special attention to molecular epidemiology, molecular diagnostics, current and new treatments, and drug resistance

Autoimmune Diseases in Patients with Premature Ovarian Insufficiency—Our Current State of Knowledge

Premature ovarian insufficiency (POI), previously known as premature ovarian failure or premature menopause, is defined as loss of ovarian function before the age of 40 years. The risk of POI before the age of 40 is 1%. Clinical symptoms develop as a result of estrogen deficiency and may include amenorrhea, oligomenorrhea, vasomotor instability (hot flushes, night sweats), sleep disturbances, vulvovaginal atrophy, altered urinary frequency, dyspareunia, low libido, and lack of energy. Most causes of POI remain undefined, however, it is estimated that anywhere from 4–30% of cases are autoimmune in origin. As the ovaries are a common target for autoimmune attacks, an autoimmune etiology of POI should always be considered, especially in the presence of anti-oocyte antibodies (AOAs), autoimmune diseases, or lymphocytic oophoritis in biopsy. POI can occur in isolation, but is often associated with other autoimmune conditions. Concordant thyroid disorders such as hypothyroidism, Hashimoto thyroiditis, and Grave’s disease are most commonly seen. Adrenal autoimmune disorders are the second most common disorders associated with POI. Among women with diabetes mellitus, POI develops in roughly 2.5%. Additionally, autoimmune-related POI can also present as part of autoimmune polyglandular syndrome (APS), a condition in which autoimmune activity causes specific endocrine organ damage. In its most common presentation (type-3), APS is associated with Hashomoto’s type thyroid antibodies and has a prevalence of 10–40%. 21OH-Antibodies in Addison’s disease (AD) can develop in association to APS-2