Recommendations of procedures to follow in the case of ovarian lesions in girls.

This study presents current recommendations of the Polish Association of Pediatric Surgeons (PTChD) regarding diagnostics and treatment of ovarian lesions in girls. They are based on many years of the authors' clinical experience as well as a review of international literature and include practical clinical guidelines. The recommendations were formulated in cooperation with the Polish Association of Pediatric Oncology and Hematology (PTOHD), Polish Pediatric and Adolescent Gynecology Section of the Polish Society of Gynecologists and Obstetricians (PTG) and Polish Pediatric Section of the Polish Society of Radiology (PLTR). Only better understanding of prepubertal ovarian biology and natural history of its pathology may help to introduce efficient and safe diagnostic and therapeutic strategies for girls. The prepared document has been supplemented with treatment algorithms.

The Immunohistochemical Expression of MCM-3, -5, and -7 Proteins in the Uterine Fibroids.

Uterine fibroids are the most common mesenchymal uterine neoplasms; their prevalence is estimated in 40%-60% of women under 35 and in 70%-80% of women over 50 years of age. The current research aims to focus on the etiopathogenesis of uterine fibroids, the factors that affect their growth, and markers with diagnostic and prognostic properties. The MCM (minichromosome maintenance) protein family consists of peptides whose primary function is participation in the molecular mechanism of creating replication forks while regulating DNA synthesis. The aim of this work was to determine the proliferative potential of uterine fibroid cells based on the expression of the Ki-67 antigen and the MCMs-i.e., MCM-3, MCM-5, and MCM-7. In addition, the expression of estrogen (ER) and progesterone (PgR) receptors was evaluated and correlated with the expression of the abovementioned observations. Ultimately, received results were analyzed in terms of clinical and pathological data. MATERIALS AND METHODS: In forty-four cases of uterine fibroids, immunohistochemical reactions were performed. A tissue microarray (TMA) technique was utilized and analyzed cases were assessed in triplicate. Immunohistochemistry was performed using antibodies against Ki-67 antigen, ER, PgR, MCM-3, MCM-5, and MCM-8 on an automated staining platform. Reactions were digitalized by a histologic scanner and quantified utilizing dedicated software for nuclear analysis. Assessment was based on quantification expression of the three histiospots, each representing one case in TMA. RESULTS: In the study group (uterine fibroids), statistically significant stronger expression of all the investigated MCMs was observed, as compared to the control group. In addition, moderate and strong positive correlations were found between all tested proliferative markers. The expression of the MCM-7 protein also correlated positively with ER and PgR. With regard to clinical and pathological data, there was a negative correlation between the expression of MCMs and the number of both pregnancies and births. Significant reductions in MCM-5 and MCM-7 expression were observed in the group of women receiving oral hormonal contraceptives, while smoking women showed an increase in MCM-7, ER, and PgR. CONCLUSIONS: Uterine fibroid cells have greater proliferative potential, as evaluated by expression of the Ki-67 antigen and MCMs, than unaltered myometrial cells of the uterine corpus. The expression of MCM-7 was found to have strong or moderate correlations in all assessed relations. In the context of the clinical data, as well evident proliferative potential of MCMs, further studies are strongly recommended.

The effects of chicken egg white cystatin and proteinase inhibitor on cysteine peptidase-like activity in the sera of patients with breast cancer.

BACKGROUND: The activity of autogenic proteolytic enzymes is regulated in vivo by autogenic inhibitors. They play important roles in maintaining a balance in many processes in the human body. In pathological conditions, enzymes are overexpressed and the balance is disturbed. Such uncontrolled changes may lead to the development of local or systemic cancer. OBJECTIVES: To evaluate the effects of specific inhibitors, i.e., chicken egg white cystatin (CEWC) and proteinase inhibitor (E-64) on autogenic cysteine peptidases (CPs) in the sera of patients reporting for subsequent stages of treatment after being diagnosed with breast cancer. Cysteine peptidases play a vital role in the basic processes that are associated with cancer progression. MATERIAL AND METHODS: We selected serum samples from 108 patients with a diagnosis of breast cancer (stages IIA-IIIA) who had received no previous treatment. The blood samples were centrifuged, and the resulting serum was placed in liquid nitrogen and stored at -80°C. The biochemical tests were performed at the laboratory of the Department of Physical Chemistry and Microbiology. RESULTS: For CEWC, we found an inhibitory effect in 37 out of 108 samples; for E-64, 14 out of 22 samples displayed an inhibitory effect. In the remaining blood samples, these inhibitors caused an increase in fluorescence. In a parallel test, we added pure cathepsin B to 9 serum samples, and then used CEWC to inhibit the activity of autogenic CPs. Chicken egg white cystatin completely inhibited the cathepsin B that was added to the serum without changing its effect on the autogenic CPs. CONCLUSIONS: The results suggest that there may be a potential difference between the commercially available cathepsin B and its autogenic analogues found in the serum of cancer patients. The increase in fluorescence induced in the reaction between the inhibitors and autogenic CPs is still unexplained. There was no relationship between the observed inhibition/activation of CPs and any of the available indicators of the health of the patients examined.

Maternal atopy and offspring epigenome-wide methylation signature.

The increase in the prevalence of allergic diseases is believed to partially depend on environmental changes. DNA methylation is a major epigenetic mechanism, which is known to respond to environmental factors. A number of studies have revealed that patterns of DNA methylation may potentially predict allergic diseases.Here, we examined how maternal atopy is associated with methylation patterns in the cord blood of neonates.We conducted an epigenome-wide association study in a cohort of 96 mother-child pairs. Pregnant women aged not more than 35 years old, not currently smoking or exposed to environmental tobacco smoke, who did not report obesity before conception were considered eligible. They were further tested for atopy. Converted DNA from cord blood was analysed using Infinium MethylationEPIC; for statistical analysis, RnBeads software was applied. Gestational age and sex were included as covariates in the final analysis.83 DM sites were associated with maternal atopy. Within the top DM sites, there were CpG sites which mapped to genes SCD, ITM2C, NT5C3A and NPEPL1. Regional analysis revealed 25 tiling regions, 4 genes, 3 CpG islands and 5 gene promoters, (including PIGCP1, ADAM3A, ZSCAN12P1) associated with maternal atopy. Gene content analysis revealed pointwise enrichments in pathways related to purine-containing compound metabolism, the G1/S transition of the mitotic cell cycle, stem cell division and cellular glucose homoeostasis.These findings suggest that maternal atopy provides a unique intrauterine environment that may constitute the first environment in which exposure is associated with methylation patterns in newborn.

Differences in cysteine peptidases-like activity in sera of patients with breast cancer.

BACKGROUND: The key role in carcinogenesis with destruction of the extracellular matrix is played by proteases released by invasive cancer cells. Cysteine peptidases, such as cathepsin B and L, take an important role in cancer progression and metastasis. OBJECTIVES: Cysteine peptidase-like activity (CPA) in sera of patients with breast cancer at different stages of disease and the influence of genetic predisposition associated with BRCA-1 gene mutations were analysed. METHODS: CPA in serum was determined with the spectrofluorometric technique using Z-Phe-Arg-AMC as a substrate. Determination was carried out in 111 breast cancer patients in comparison to a control group of 50 healthy subjects. RESULTS: The highest CPA was found in breast cancer patients with a hereditary predisposition bearing BRCA1 gene mutations, and the lowest activity was found in patients who had a tumour surgically removed and before adjuvant therapy. The differences in the activities between control group and cancer groups were statistically significant (p< 0.05), except from group of cancer patients in complete remission (p< 0.52). CONCLUSIONS: Serum CPA in patients with breast cancer differs depending on the cancer stage and treatment methods. Our study demonstrate the correlation between BRCA-1 gene mutations and the increased level of CPA.

Is polycystic ovarian syndrome and insulin resistance associated with abnormal uterine bleeding in adolescents?

OBJECTIVES: The aim of the study was to determine if adolescents with juvenile bleeding had polycystic ovarian syndrome (PCOS) and insulin resistance. MATERIAL AND METHODS: The study was conducted in a group of 43 females aged 12-18 years, diagnosed with juvenile menorrhagia, and 37 healthy female adolescents aged 12-18 years. The study was conducted during the early follicular phase of the menstrual cycle. Menstrual cycle disturbances, acne and hirsutism were recorded. Ultrasound scan determining the condition of the ovaries was conducted. Laboratory tests of the glucose level, cholesterol, LDL and HDL cholesterol and triglycerides fraction, DHEAS, FSH, LH, insulin, SHGB, total testosterone, androstenedione, and free testosterone have been established. RESULTS: The occurrence of regular menstrual cycles (30.23%, p = 0.006) was significantly lower in the juvenile bleeding group. Also, secondary amenorrhea was significantly more likely to be recognized in this group of females (p = 0.03). The concentration of FSH was considerably lower (p = 0.0002) in the group of adolescents with AUB. CONCLUSIONS: Adolescents with abnormal uterine bleeding (AUB) are often diagnosed with secondary amenorrhea, and PCOS. The group with a diagnosis of juvenile bleeding was also diagnosed with higher rates of insulin resistance.

The Usefulness of Immunohistochemistry in the Differential Diagnosis of Lesions Originating from the Myometrium.

Uterine leiomyomas (LMs), currently the most common gynecological complaint around the world, are a serious medical, social and economic problem. Accurate diagnosis is the necessary prerequisite of the diagnostic-therapeutic process. Statistically, mistakes may occur more often in case of disease entities with high prevalence rates. Histopathology, based on increasingly advanced immunohistochemistry methods, is routinely used in the diagnosis of neoplastic diseases. Markers of the highest sensitivity and specificity profiles are used in the process. As far as LMs are concerned, the crux of the matter is to identify patients with seemingly benign lesions which turn out to be suspicious (e.g., atypical LM) or malignant (e.g., leiomyosarcoma (LMS)), which is not uncommon. In this study, we present the current state of knowledge about the use of immunohistochemical markers in the differential diagnosis of LM, atypical LM, smooth muscle tumors of uncertain malignant potential (STUMP), and LMS, as well as their clinical predictive value.

Association of serum glypican-4 levels with cardiovascular risk predictors in women with polycystic ovary syndrome - a pilot study.

OBJECTIVE: Glypican-4 (Gpc4) is an adipokine which interacts with the insulin receptor and affects insulin sensitivity in proteoglycans. Insulin resistance plays a crucial role in the etiology of polycystic ovary syndrome (PCOS). PCOS is associated with metabolic disturbances such as abdominal obesity, dyslipidemia and type 2 diabetes. Thus, higher levels of Gpc4 released from visceral adipose tissue in women with PCOS may suggest an increased risk of cardiovascular disease (CVD). DESIGN: The aim of this pilot study was to determine whether the serum Gpc4 level is associated with cardiovascular risk predictors in women with PCOS. METHODS: Sixty-two women with PCOS according to the Rotterdam criteria (20-35 years old) and 43 healthy controls were studied. Cardiovascular risk predictors such as obesity indices, fat deposits according to dual-energy X-ray absorptiometry, biochemical lipid profile parameters and Homeostasis Model Assessment were estimated. RESULTS: The serum Gpc4 level in PCOS women was significantly higher (2.61 ± 1.17 ng/ml) than in the control group (1.55 ± 0.47 ng/ml) and correlated with waist circumference, waist-to-hip ratio, total fat and android fat deposit to gynoid fat deposit ratio only in the PCOS group. CONCLUSION: The Gpc4 level was higher in the PCOS group and correlated with CVD risk predictors, especially fat distribution.

Classic PCOS phenotype is not associated with deficiency of endogenous vitamin D and VDR gene polymorphisms rs731236 (TaqI), rs7975232 (ApaI), rs1544410 (BsmI), rs10735810 (FokI): a case-control study of lower Silesian women.

CONTEXT: The role of endogenous vitamin D and vitamin D receptor (VDR) gene polymorphism in polycystic ovary syndrome (PCOS) is still controversial. OBJECTIVE: The objective of this study was to investigate for the first time in women with "classic" PCOS phenotype and healthy controls the role of the serum endogenous vitamin D level and VDR gene polymorphisms in PCOS etiology. DESIGN: Ninety-two women with "classic" PCOS phenotype and 85 controls from lower Silesia with comparable body mass index (BMI) were studied. In all women the waist circumference, android/gynoid fat deposit, parameters of lipid and glucose metabolism, testosterone, free androgen index, sex hormone binding globulin (SHBG) and vitamin D were evaluated. Also, VDR gene polymorphisms rs731236, rs7975232, rs1544410 and rs10735810 were assessed. RESULTS: Serum vitamin D levels in both groups were comparable. Also high, comparable frequencies of hypovitaminosis and vitamin D deficiency in both groups were observed. Women with "classic" PCOS phenotype had statistically significantly higher values of all measured parameters, except serum SHBG and high-density lipoprotein (HDL)-cholesterol, which were lower. The frequency of VDR genotype polymorphism was also comparable in both groups. CONCLUSIONS: For the first time, we show that endogenous vitamin D deficiency and VDR polymorphisms are not associated with homogeneous "classic" PCOS phenotype.

O-glycosylation of α-1-acid glycoprotein of human milk is lactation stage related.

BACKGROUND: Human milk provides a multitude of glycoproteins, including highly glycosylated α-1-acid glycoprotein (AGP), which elicits anti-inflammatory and immunomodulatory properties. The milk AGP glycoforms may provide the breastfed infant with a wide range of biological benefits. Here, we analyzed the reactivity of O-linked sugar-specific lectins with human milk AGP over the process of lactation and compared the results with those of the lactating mother's plasma. MATERIALS AND METHODS: Relative amounts of human skim milk AGP O-glycans were analyzed in early colostrum, colostrum, and transitional and mature milk samples of 127 healthy mothers by lectin-AGP enzyme-linked immunosorbent assay using sialyl T (sialyl-α2,3/α2,6 Galß1,3GalNAc-), asialyl T (Galß1,3GalNAc-), and Tn (GalNAc-) antigen-specific biotinylated Artocarpus integrifolia (Jacalin), Arachis hypogaea (PNA), and Vicia villosa (VVA) lectins, respectively. RESULTS: Milk AGP elicited high expression of Jacalin- and PNA-reactive glycotopes and low expression of VVA-reactive glycotopes, which were absent on plasma AGP of lactating mothers and healthy individuals. The expression of sialyl, asialyl T, and Tn glycotopes of human milk AGP was lactation stage related. The relative amount of Jacalin-reactive AGP glycotope was highest in the colostrum samples and then decreased starting from Day 8 of lactation. In contrast, an increase of the relative amount of PNA-reactive glycotope with milk maturation was observed. The relative amount of VVA-reactive glycotope remained almost constant over the development of lactation. CONCLUSIONS: Milk AGP differs from mother's plasma AGP by the presence of O-linked sialylated and asialylated T as well as Tn antigens. The variation of the expression of sialylated and asialylated T and Tn antigens on AGP is associated with milk maturation.

Selected CNR1 polymorphisms and hyperandrogenemia as well as fat mass and fat distribution in women with polycystic ovary syndrome.

The endocannabinoid system is postulated to play an important role in the etiology of obesity, insulin resistance, fat distribution and metabolic disorders. Insulin resistance associated with abdominal obesity plays a leading role in the etiology of hyperandrogenism and other clinical features of the polycystic ovary syndrome (PCOS). A total of 174 women 16-38 years old, diagnosed with PCOS according to the Rotterdam criteria are recruited. Control group consisted of 125 healthy women 18-45 years old. Medical history, physical examination, anthropometric parameters and metabolic parameters were carried out. Six CNR1 gene polymorphisms were diagnosed. We observed a significantly three times higher risk of GG genotype in the polymorphism rs12720071 in women with PCOS versus the control group (p = 0.0344, OR = 3.01). A similar, significant 8-fold higher risk (p = 0.0176, OR = 8.81) was demonstrated for genotype CC polymorphism rs806368 associated with PCOS. We observed a 3.6-fold increased risk of hyperandrogenemia (free androgen index - FAI > 7) in patients with GG genotype in the rs12720071 polymorphism and AA genotype in the polymorphism rs1049353 (OR = 2.7). Our study may indicate a role of the endocannabinoid system in the occurrence of a specific hyperandrogenemia phenotype of PCOS.

Anal warts (condylomata acuminata) - current issues and treatment modalities.

HPV infections are currently the most frequent cause of genital infections in the USA. Risk factors are early onset of sexual activity, multiple sexual partners, a history STDs, an early age of first pregnancy and tobacco use. In the past, HPV viruses were thought to be STDs, but it is now known that penetration is not necessary. Skin-to-skin or mucosa-to-mucosa contact is enough to transmit the virus, which presents high tropism for those tissues. The Papillomaviridae family includes over 120 viruses, some of which have high malignant transformation rates. The most common malignancy connected to HPV is uterine cervix cancer and anal canal cancer. The range of morphology of perianal lesions means that a thorough clinical examination is required, including an anoscopy. Therapeutic modalities often seek to eliminate macroscopic changes rather than focus on the cause of the infection, which leads to a high recurrence rate. Externally located changes can be eliminated with patient-applied treatments. Those located in the anal canal and distal end of the rectal ampulla require treatment by a qualified medical provider. Due to the high recurrence rate after standard treatment, special attention has been given to vaccinations. The polyvalent vaccine includes HPV viruses with both low and high malignant transformation risk. This has led to a decrease in the rate of malignancies.