Functional evidence for two distinct mechanisms of action of progesterone and selective progesterone receptor modulator on uterine leiomyomas.

OBJECTIVE: To study the specific mechanisms through which progesterone and selective progesterone receptor modulators impact the growth, synthesis, and accumulation of the extracellular matrix in uterine leiomyomas. DESIGN: Laboratory study. SETTING: Academic Research Institutions. PATIENTS (S): This study involved reproductive-age women diagnosed with infertility associated uterine leiomyomas who underwent myomectomy either after selective progesterone receptor modulator ulipristal acetate (UA) treatment or without any pharmacological pretreatment. Control samples included healthy myometrium tissue (n = 100). Specimens were obtained from the Department of Reproduction and Gynecological Endocrinology and Biobank, Medical University of Bialystok, Poland. INTERVENTIONS: Daily (5 mg/d) UA treated for 2 months (n = 100) and untreated (n = 150) patients with uterine leiomyomas or normal healthy myometrium (n = 100) tissue samples immediately after surgery were collected for transcriptional analysis and assessments. MAIN OUTCOME MEASURES: Progesterone-induced activation of the signaling pathways related to uterine leiomyomas extracellular matrix synthesis, deposition, and growth, as well as the expression profile of progesterone receptors in uterine leiomyomas, were assessed. RESULTS: The results indicated that progesterone activated the transforming growth factor-ß and SMAD3 signaling pathways and promoted proliferation, growth, and extracellular matrix remodeling in uterine leiomyomas by up-regulating SMAD3, transforming growth factor-ß (TGF-ß) receptor type 1 and II, Ras homolog A, vascular endothelial growth factor, or increasing the fibrosis-related gene collagen, type I, ɑ-1, and procollagen, type I, ɑ-1 production. In contrast, UA had inhibitory effects on these processes. The study also showed that both nuclear and membrane progesterone receptors play distinct roles in uterine leiomyoma pathobiology. CONCLUSIONS: We showed that both nuclear and membrane progesterone receptors were relevant in the treatment of uterine leiomyomas, especially when combined with selective progesterone receptor modulators. Novel therapeutic approaches combining selective progesterone receptor modulators with or without direct and indirect extracellular matrix targeting through selected specifically TGF-ß and SMAD3 (SMAD3, TGF-ß receptor types 1 and II, Ras homolog A, vascular endothelial growth factor, collagen, type I, ɑ-1) signaling pathways could therefore be a treatment option for uterine leiomyomas.

Progesterone signaling in uterine leiomyoma biology: Implications for potential targeted therapy.

Uterine leiomyomas (ULs) are the most common benign smooth muscle cell steroid-dependent tumors that occur in women of reproductive age. Progesterone (P4) is a major hormone that promotes the ULs development and growth. P4 action in ULs is mediated mainly by its nuclear progesterone receptors (PGRs), although rapid non-genomic responses have also been observed. Data on the membrane progesterone receptors (mPRs) regulated signaling pathways in ULs in the available literature is still very limited. One of the essential characteristics of ULs is the excessive production of extracellular matrix (ECM). P4 has been shown to stimulate ECM production and collagen synthesis in ULs. Recent research demonstrated that, despite their benign nature, ULs may present with abnormal vasculature. P4 has been shown to regulate angiogenesis in ULs through the upregulation of vascular endothelial growth factor (VEGF) and by controlling the secretion of permeability factors. This review summarizes the key findings regarding the role of PGRs and mPRs in ULs, especially highlighting the potential ECM and angiogenesis modulation by P4. An increased understanding of this mechanistic role of nuclear and specifically mPRs in the biology of P4-modulated ECM and angiogenesis in the growth of ULs could turn out to be fundamental for developing effective targeted therapies for ULs.

Effects of drought on environmental health risk posed by groundwater contamination.

This publication presents a comparison of the content of pollutants in groundwater samples taken at 117 measurement points in four regions of Poland during a drought period and in the reference period without drought. Based on the chemical analyses of water, an assessment of the health risk resulting from the use of underground water for consumption was carried out. The study aimed to determine whether drought affects the increase in health risk exposure of the population. It was found that despite the occurrence of drought, the expected increase in the concentration of pollutants in water does not take place in all locations. This study found that in some cases the occurrence of drought did not cause an increase in the non-cancerogenic threat expressed by the hazard index. There were also no clear changes in excess lifetime cancer risk values except for selected measurement points. On the other hand, the statistical analysis of all data collected in the regions where the research was conducted showed a general trend of increasing environmental health risk caused by changes in groundwater pollution during drought.

Environmental health risk posed by contamination of the individual water wells.

This paper presents the results of analyzes of water samples taken from individual water wells intended for supplying households in non-urbanized areas with low population and infrastructure density. Relatively high concentrations of harmful pollutants were found in ground waters of the examined spots located in the suburban areas which may increase the risk of health incidents in exposed populations. Based on long-term measurements carried out in individual spots and toxicological data, the individual health risks related to carcinogenic effects in humans were assessed, resulting from direct ingestion of such water and from dermal contact. Non-carcinogenic hazard levels were determined, as well. In this work a novel approach to health risk assessment was proposed. It consists of determining the risks that range between minimum and possible maximum values. In the case of limited traceability of a pollutant the maximum and minimum risk values were derived from the limit of quantification (LOQ). Thus, for the minimum risk, zero concentration was applied, while for calculation of the maximum risk, LOQ was used as the possible highest pollutant content in water. The calculations proved that using untreated water for consumption and bathing is likely to cause an increase of both mutagenic and toxic risk in humans concerned. Depending on the site, the calculated non-carcinogenic hazard level expressed by the hazard index HI ranges between 0.6 and 3.6 while the excess lifetime cancer risk ELCR is of the order of 10-4.

Identifying risk sources of air contamination by polycyclic aromatic hydrocarbons.

This article is directed to determining concentrations of polycyclic aromatic hydrocarbons (PAHs), which are sorbed to solid particles in the air. Pollution sources were identified on the basis of the ratio of benzo[ghi]perylene (BghiPe) to benzo[a]pyrene (BaP). Because various important information is lost by determining the simple ratio of concentrations, least squares linear regression (classic ordinary least squares regression), reduced major axis, orthogonal regression, and Kendall-Theil robust diagnostics were utilized for identification. Statistical evaluation using all aforementioned methods demonstrated different ratios of the monitored PAHs in the intervals examined during warmer and colder periods. Analogous outputs were provided by comparing gradients of the emission factors acquired from the measured concentrations of BghiPe and BaP in motor vehicle exhaust gases. Based on these outputs, it was possible plausibly to state that the influence of burning organic fuels in heating stoves is prevalent in colder periods whereas in warmer periods transport was the exclusive source because other sources of PAH emissions were not found in the examined locations.

Chemical elimination of the harmful properties of asbestos from military facilities.

This work presents research on the neutralization of asbestos banned from military use and its conversion to usable products. The studies showed that asbestos can be decomposed by the use of phosphoric acid. The process proved very effective when the phosphoric acid concentration was 30%, the temperature was 90°C and the reaction time 60min. Contrary to the common asbestos treatment method that consists of landfilling, the proposed process ensures elimination of the harmful properties of this waste material and its transformation into inert substances. The obtained products include calcium phosphate, magnesium phosphate and silica. Chemical, microscopic and X-ray analyses proved that the products are free of harmful fibers and can be, in particular, utilized for fertilizers production. The obtained results may contribute to development of an asbestos utilization technique that fits well into the European waste policy, regulated by the EU waste management law.

Determinants of emotional problems and mood disorders in women with polycystic ovary syndrome.

OBJECTIVES: The aim of the study was to assess the prevalence and severity of emotional problems among Polish women with polycystic ovary syndrome (PCOS) and seek factors which increase the risk of their occurrence. MATERIAL AND METHODS: The study group consisted of 82 women (aged 18-48), who were diagnosed with PCOS based on the Rotterdam criteria. During hospitalization, the patients completed a number of questionnaires, providing their sociodemographic data and information concerning the inconvenience of disease-associated symptoms. The question-naires included the Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), and Multidimensional Self-Esteem Inventory (MSEI). Data obtained during medical examinations (blood tests, transvaginal ultrasound, height and body mass measurements) were analyzed. RESULTS: Out of 82 women, the results detected risk for depression in 42 (51.22%), mild depressive disorders in 32, moderate disorders in 8, and severe disorder in 2 patients. No statistically significant correlation between BDI or state anxiety and the level of the analyzed hormones, insulin resistance, or infertility treatment, was found. General self-esteem, trait anxi-ety, and marital status were associated with the occurrence of depression symptoms. BMI was associated with the level of state anxiety during hospitalization. CONCLUSIONS: Women with PCOS are at risk for mood and anxiety disorders. Disease-related somatic factors are not directly associated with the risk for disorder occurrence. However, severity of depression symptoms has been shown to be influenced by permanent psychological characteristics of the studied women, i.e. self-esteem, trait anxiety, and life situation (marital status). Therefore, it is recommended to include interviews about patient life situation and screening questionnaires for assessing depression into the diagnostic procedures in PCOS patients. Patients should be referred for a psychological or psychiatric consultation, if needed.

Impact of military metallurgical plant wastes on the population's health risk.

This paper presents the results of water, soil and air analyses taken in the vicinity of a former ferrochromium metallurgical plant. In the past, the area was used for the disposal of waste materials containing smelter slag, dust and other waste products from the manufacture of ferrochromium alloys for the army. Recently, production was abandoned and a project aimed at the liquidation of the dump has been initiated. The project concentrates on the recovery of chromium remains and the utilization of the leftover material as a road construction aggregate. Based on the analyses of ground water, soil and air, a health risk caused by environmental pollution with chromium, especially with Cr(VI), was determined for residential and occupational scenarios. It was found that the level of chromium emissions to the environment constitutes a potential danger of toxic and carcinogenic cases in humans exposed to the emission in the affected area. An increased level in the hazard quotient has been observed in the case of occupational activities. As far as the mutagenic effects are concerned, the occupational inhalation exposure was found to be very high, which may raise extreme concern about carcinogenic risk.

Health risk associated with airborne asbestos.

The following paper presents an assessment of health risks associated with air polluted with respirable asbestos fibers in towns of southwest Poland. The aim of the work was to determine whether or not any prevention measures are necessary in order to reduce the level of exposure to the pollutant. The risk assessment was carried out based on the air analyses and the latest asbestos toxicity data published by the Environmental Protection Agency (US EPA), USA and Office of Environmental Health Hazard Assessment (OEHHA). It was found that in some sites, the concentration of the asbestos fibers exceeded the acceptable levels, which should be a reason of special concern. The highest concentration of asbestos was found in town centers during the rush hours. In three spots, the calculated maximum health risk exceeded 1E-04 which is considered too high according to the adopted standards. So far, it has not yet been possible to find a reasonable method of ensuring the hazard reduction.

Assessment of health risk associated with persistent organic pollutants in water.

This paper presents the results of analyses of water samples taken from water intakes supplying one of the districts located near the city of Wroclaw. Surprisingly high concentrations of polychlorinated biphenyls and chloroorganic pesticides, classified as persistent organic pollutants (POPs), were detected in the monitored sites. Basing on the analytical and toxicological data, the individual health risks related to carcinogenic effects (excess cancer risk over a lifetime) in humans were assessed, resulting from direct ingestion of community water. Also noncarcinogenic effects resulting from exposure to the examined POPs were determined. The conservative approach to risk assessment, taking into account a safety margin for data incompleteness, was adopted. The carcinogenic risk was found to slightly exceed the unconditionally acceptable risk of 10(-6) in the case of polychlorinated biphenyls and hexachlorocyclohexane, for all the inhabitant populations. The determined values of noncarcinogenic effects expressed by hazard quotient and hazard index indicate that the water pollutants and their concentrations do not cause an increase in noncarcinogenic incidences in the inhabitants using the monitored water sources.

Assessment of health hazard associated with nitrogen compounds in water.

This paper presents results of analyses of water in the river Mala Panew in South West Poland flowing through a rural area with some chemical industry developed. The aims of the work were to investigate the pollutants level in the river, compare the obtained results with obligatory drinking water standards and determine possible health effects when using the river as a source for drinking water production. Attention was given to nitrogen compounds as nitrate(V) ions (NO(3-)) and nitrite(III) ions (NO(2-)), mostly of anthropogenic origin, were detected in the monitored water. The average concentrations of NO(3-) and NO(2-) were 3.54 and 0.286 mg/dm(3), respectively. The chances for non-carcinogenic effects, namely methemoglobinemia, resulting from possible exposure to the examined chemicals were determined based on the analytical and toxicological data. As infants are the sub-population most susceptible to nitrate-induced methemoglobinemia, the assessment was limited to children aged 0-3 years. The determined values expressed by hazard quotient (HQ) and hazard index (HI) indicate that the water pollutants and their concentrations do not exceed unity; however, in the case of infants, the other nitrate sources should be controlled.