Core-Shell Nanocables Decorated with Carbon Spherical Shells and Silver Nanoparticles for Sensing Ethinylestradiol Hormone in Water Sources and Pills.

The selective, rapid detection of low levels of hormones in drinking water and foodstuffs requires materials suitable for inexpensive sensing platforms. We report on core-shell Ag@C nanocables (NCs) decorated with carbon spherical shells (CSSs) and silver nanoparticles (AgNPs) by using a hydrothermal green approach. Sensors were fabricated with homogeneous, porous films on screen-printed electrodes, which comprised a 115 nm silver core covered by a 122 nm thick carbon layer and CSSs with 168 nm in diameter. NCs and CSSs were also decorated with 10-25 nm AgNPs. The NC/CSS/AgNP sensor was used to detect ethinylestradiol using square wave voltammetry in 0.1 M phosphate buffer (pH 7.0) over the 1.0-10.0 µM linear range with a detection limit of 0.76 µM. The sensor was then applied to detect ethinylestradiol in tap water samples and a contraceptive pill with recovery percentages between 93 and 101%. The high performance in terms of sensitivity and selectivity for hormones is attributed to the synergy between the carbon nanomaterials and AgNPs, which not only increased the sensor surface area and provided sites for electron exchange but also imparted an increased surface area.

Histological investigation in aging male and female gerbil prostates after prenatal exposure to pequi (Caryocar brasiliense Cambess) oil and 17α-ethinylestradiol.

The female prostate, also known as Skene's gland, is present in both humans and rodents. Prenatal exposure to ethinylestradiol (EE2), a synthetic estrogen found in oral contraceptives, induces pormotes neoplasic prostate lesions in gerbils (Meriones unguiculatus). Conversely, pequi oil (Pe), extracted from the Brazilian Cerrado fruit, has antioxidant, anti-inflammatory, and anticancer properties, mitigates risks associated with chronic diseases related to lifestyle and aging. This study evaluates the impact of prenatal exposure to Pe (300 mg/kg) on senile gerbil offspring's male and female prostates under normal conditions and EE2 exposure (15 µg/kg/day). Histological and morphometric analyses revealed that Pe reduced male body weight and prostate epithelial height, along with a thinner muscle layer. In females, EE2 exposure reduced prostatic weight, while Pe exposure lowered epithelial height and the relative stromal compartment volume, increasing the muscle layer. Pequi oil holds potential in mitigating alterations induced by exposure to the endocrine disruptor EE2.

The influence of aeration rate on the sorption of emerging pharmaceuticals in activated sludge.

The sorption of pharmaceuticals on activated sludge during the wastewater treatment process has been widely studied and considered one of the main mechanisms for the removal of these micropollutants from domestic sewage. Understanding the removal mechanism is important to reduce the environmental risk associated with these compounds. To the best of our knowledge, no data are reporting the influence of the aeration rate and, consequently, of the physicochemical properties of the sludge flocs, on the sorption of pharmaceutical compounds. In this context, the influence of the aeration rate (2, 5, and 8 L min-1) on the physical properties of the sludge and the sorption of two emerging pharmaceuticals, 17-alpha-ethynylestradiol (EE2) and diclofenac (DCF), was evaluated. The pharmaceuticals were analyzed by Solid Phase Extraction and Liquid Chromatography, and the sludge by Laser Particle Size Analyzer and Settling Curves. As a result, higher sorption for 17-alpha-ethinylestradiol (78-96%) in comparison to diclofenac (23-43%) was observed, corroborating the greater hydrophobicity of EE2. Higher pharmaceuticals removal rates were observed for the highest aeration (10.02 µgEE2 gSST-1 and 3.99 µgDCF gSST-1) in comparison to the lowest one (7.81 µgEE2 gSST-1 and 2.58 µgDCF gSST-1), what can be attributed to structural and surface changes in flocs. Smaller and more dispersed flocs were observed when aeration was increased (104.4 µm for 8 L min-1 and 63.8 µm for 2 L min-1). The results suggest that the increase in aeration seems to be promising for the removal of pharmaceuticals by sorption in sewage sludge, especially for the hydrophobic ones.

Combined reverse osmosis and UV/H2O2 treatment of aqueous solutions of bisphenol A and 17α-ethinylestradiol: assessment of estrogenic activity.

Bisphenol-A (BPA) and 17α-ethinylestradiol (EE2) are considered endocrine disrupting compounds (EDC) and they may be harmful to the normal functioning of endocrine systems of humans and animals. Moreover, the presence of these compounds in superficial and groundwater may represent serious risks, even in low concentrations like ng·L-1. The objectives of this study were to remove BPA and EE2 from solutions containing a mixture of these compounds in ultrapure water at low concentrations through reverse osmosis (RO) membrane combined with a UV/H2O2 process. Furthermore, to assess the estrogenic activity reduction after such treatments, in vitro recombinant yeast-estrogen screen (YES) assay was used. The removal efficiencies of target micropollutants increased with the increase of H2O2 dosage. For RO permeate stream, they enhanced from 91% to 96% for EE2 and from 76% to 90% for BPA while, for the concentrate stream, from 70% to 81% for EE2 and 41% to 84% for BPA as the H2O2 concentration were increased from 100 to 1000 µg·L-1. The OH radicals' generation was the dominant factor in the degradation of EDC during the UV/H2O2 treatment since the photolysis itself was not enough to degrade BPA or EE2. The estrogenic activity reduction after UV/H2O2 treatment was high, ranging from 92% to 98% for the permeate stream and from 50% to 93% for the concentrate stream. The EE2 was responsible for the whole observed estrogenic activity since BPA does not present estrogenicity, by in vitro YES assay, in the concentrations observed.

Effect of Norelgestromin and Ethinylestradiol in Transdermal Patches on the Clinical Outcomes and Biochemical Parameters of COVID-19 Patients: A Clinical Trial Pilot Study.

The disease caused by SARS-CoV-2 is still considered a global pandemic. Transdermal patches (TP) with immunoregulators such as estrogen and progesterone compounds could be a feasible option to treat COVID-19 because of their accessibility and relative safety. The objective of the current study was to evaluate the additional treatment with norelgestromin and ethinylestradiol in TP on the clinical and biochemical evolution of COVID-19 patients. The present is a clinical-trial pilot study that included subjects diagnosed with COVID-19, randomized into two groups; the experimental Evra® TP (norelgestromin 6 mg and ethinylestradiol 0.60 mg) was administered such that it was applied on arrival and replaced at day 8 and day 15. The control continued with the conventional COVID-19 treatment protocol. A blood sample was taken each week in order to evaluate relevant biochemical parameters, clinical signs, and evolution. In total, 44 subjects participated in this study, 30 in the experimental group and 14 in the control group. Both groups were homogeneous in terms of age and comorbidities. The experimental group had a significantly lower hospital stay (p = 0.01), high flow supplemental oxygen (p = 0.001), mechanical ventilation (p = 0.003), and intubation (p = 0.01), and the oxygen saturation significantly increased (p = 0.01) in comparison with control group when patients were exposed to room air. A decrease in ferritin (p < 0.05) was observed, with no significant increase in ESR (p > 0.05), D dimer (p > 0.05) and platelets (p > 0.05) in an auto-controlled analysis in the experimental group. Norelgestromin and ethinylestradiol TP could be a safe and effective treatment for moderate and severe COVID-19 patients.

Hydroxypropyl methylcellulose-sugarcane bagasse adsorbents for removal of 17α-ethinylestradiol from aqueous solution and freshwater.

Adsorbents made of hydroxypropyl methylcellulose (HPMC) and sugarcane bagasse (BG) microparticles were applied for the separation of 17α-ethinylestradiol (EE2) from aqueous solution in batch, and from aqueous solution and freshwater in fixed-bed columns. HPMC chains and BG microparticles were crosslinked by the esterification with citric acid. The adsorbents presented compression modulus values that increased from 208 ± 20 kPa (pure HPMC) to 917 ± 90 kPa, when the content of BG particles added to HPMC was 50 wt% (HPMC50BG). The porosity (~ 97%), specific surface area (1.16 ± 0.10 m2/g) and swelling degree (20 ± 1 g water/g) values were not affected by the addition of BG particles. The adsorption isotherms determined for EE2 on HPMC and on HPMC50BG fitted to the Langmuir and Freundlich models; the adsorption capacity of HPMC was slightly higher than that of composite HPMC50BG. Nevertheless, the addition of BG particles rendered outstanding mechanical reinforcement and dimensional stability to the adsorbents. The adsorption was driven by (i) hydrophobic interactions between EE2 methylene and aromatic groups and HPMC methyl groups, as evidenced by FTIR spectroscopy, and (ii) H bonds between HPMC and EE2 hydroxyl groups, as revealed by the adsorption enthalpy change (ΔHads) of - 45 kJ/mol. Column adsorption experiments of EE2 from aqueous solution on HPMC and HPMC50BG indicated adsorptive capacity (q0) values of 8.06 mg/g and 4.07 mg/g, respectively. These values decreased considerably for the adsorption of EE2 from river water, probably due to the competition of EE2 with humic substances dissolved in natural water. The HPMC adsorbents could be recycled retaining up to 83% of the original efficiency.

Assessment of fouling mechanisms on reverse osmosis (RO) membrane during permeation of 17α-ethinylestradiol (EE2) solutions.

Fouling mechanisms are mainly caused by the deposition of organic compounds that reduce the removal efficiency on reverse osmosis (RO) membranes. It can be described by mathematical models. The aim of this study was to evaluate the membrane fouling and rejection mechanisms when aqueous solutions containing 17α-ethinylestradiol (EE2) in different concentrations are permeated at 5 and 10 bar in a bench-scale dead-end RO system. Adsorption tests were performed and the fouling mechanism was assessed by Hermia's model for solutions of EE2 at concentrations typically found in the environment (µg L-1). Fourier transform infrared spectroscopy (FTIR) has indicated the presence of EE2 on the fouled membrane surface. Membrane rejection of EE2 ranged from 90% to 98% and the main rejection mechanism was size exclusion at all experimental conditions. However, for the higher concentration of EE2 permeated at 5 and 10 bar, adsorption of 7 and 32 mg m-2, respectively, also took place. The rejection was influenced by fouling and concentration polarisation. Fouled membranes present higher rejection of hydrophobic neutral compounds and the concentration polarisation reduces rejection. Hermia's model demonstrated that the permeation values fitted better the standard blocking filtration and cake filtration equations for describing fouling mechanism. This study showed that fouling also occurs in the TFC RO membrane after permeation of EE2, which corroborates with studies using other pollutants.

Pharmacokinetics of oral levonorgestrel and ethinylestradiol in women after Roux-en-Y gastric bypass surgery.

BACKGROUND: Most patients undergoing Roux-en-Y gastric bypass (RYGB) are women in reproductive age. It is not known if bariatric surgery affects the pharmacokinetics of oral contraceptives. OBJECTIVES: The primary objective was to evaluate ethinylestradiol (EE) and levonorgestrel (LNG) absorption in women undergoing RYGB, compared with nonoperated controls matched by age and body mass index (BMI). A secondary objective was to assess whether the time since surgery and BMI in the postoperative period influenced the absorption parameters. SETTING: University hospital, Brazil. METHODS: This study was designed to compare the maximum plasma concentration (Cmax), the time to the peak plasma level (Tmax), the area under the curve (AUC0-8 and AUC0-∞) after a single dose of a combined oral contraceptive with 0.03 mg EE and 0.15 mg LNG among 20 women after RYGB and 20 controls. Blood samples were obtained for 8 hours. RESULTS: The mean LNG AUC0-8 and LNG AUC0-∞ were higher in RYGB group (P = .048 and P = .004, respectively). We found a positive correlation for LNG AUC0-8 (P = .045) and AUC0-∞ (P = .004) and the time since surgery, and we found a negative correlation for LNG Cmax (P = .018), AUC0-8 (P = .003), and AUC0-∞ (P = .001) and BMI. CONCLUSION: No significant differences were found in oral EE pharmacokinetics. The operated group showed higher mean LNG AUC0-8 and AUC0-∞ but it was not considered clinically significant. The present study suggests that RYGB may not affect EE and LNG absorption.

A comparative study of persulfate activation by iron-modified diatomite and traditional processes for the treatment of 17α-ethinylestradiol in water.

Emerging pollutants have been the subject of worldwide study because their continuous entry into the environment presents a risk to ecosystems and human health. Advanced oxidation processes show promise for eliminating or reducing the concentrations of emerging pollutants in water. This study aimed to investigate the treatment of aqueous systems containing the synthetic hormone 17α-ethinylestradiol. An innovative method for persulfate activation catalysed by iron-modified diatomite (heterogeneous system) was compared to conventional homogeneous activation methods (iron activation, alkaline activation, and heat activation). Iron-modified diatomite was more efficient in activating persulfate than traditional processes, achieving 98% of pollutant removal. Experimental results indicated that the catalyst can be reused without loss of removal efficiency, with potential environmental and economic benefits.

Voltammetric determination of ethinylestradiol using screen-printed electrode modified with functionalized graphene, graphene quantum dots and magnetic nanoparticles coated with molecularly imprinted polymers.

The present work reports the development of a sensitive and selective method for ethinylestradiol detection using screen-printed electrode (SPE) modified with functionalized graphene (FG), graphene quantum dots (GQDs) and magnetic nanoparticles coated with molecularly imprinted polymers (mag@MIP). The performance of the mag@MIP sensor was compared with that of a non-molecularly imprinted sensor (mag@NIP). Chemical and physical characterizations of the mag@NIP and mag@MIP sensors were performed using scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and Brunauer-Emmett-Teller (BET) techniques. The electrochemical behavior of the electrodes investigated, which included (mag@MIP)-GQDs-FG-NF/SPE, (mag@NIP)-GQDs-FG-NF/SPE, GQDs-FG-NF/SPE and FG-NF/SPE, was evaluated by cyclic voltammetry. The results obtained show a significant increase in peak current magnitude for (mag@MIP)-GQDs-FG-NF/SPE. Using square wave voltammetry experiments, the efficiency of the (mag@MIP)-GQDs-FG-NF/SPE sensor was also tested under optimized conditions. The linear response range obtained for ethinylestradiol concentration was 10 nmol L-1 to 2.5 µmol L-1, with limit of detection of 2.6 nmol L-1. The analytical signal of the (mag@MIP)-GQDs-FG-NF/SPE sensor suffered no interference from different compounds and the sensor exhibited good repeatability. The proposed sensor was successfully applied for ethynilestradiol detection in river water, serum and urine samples, where recovery rates between 96 to 105% and 97-104% were obtained for environmental and biological samples, respectively.

Development of a portable electroanalytical method using nickel modified screen-printed carbon electrode for ethinylestradiol determination in organic fertilizers.

Urine and struvite are organic fertilizers that have all nutritional requirements for the growth of a plant. However, these fertilizers may contain some emerging organic contaminants, such as ethinylestradiol, which is one of the most common hormones found in aquatic environments and can cause several changes in living organisms. Thus, the present study developed a fast, sensitive, inexpensive, and portable method for determining ethinylestradiol in urine and struvite, using square wave voltammetry (SWV) and screen-printed carbon electrodes modified with electrodeposited nickel film (SPCE-Ni). The electrodeposition of the nickel film on the screen-printed electrode was performed by cyclic voltammetry and optimized using complete factorial design 23 and central composite design. The parameters optimized for SPCE-Ni were: number of cycles (1000); scan rate (5 V s-1) and Ni2+ concentration (9.4 mmol L-1). The operational parameters of the SWV for ethinylestradiol analysis were also optimized by experimental designs and obtained the following optimal values: step potential (10 mV), modulation amplitude (40 mV), and frequency (20 Hz). The method used 0.1 mol L-1 BR buffer (pH 8.0) as support electrolyte and presented a limit of detection of 0.052 µmol L-1 (R2 = 0.996). Ethinylestradiol recovery test in struvite, human urine, synthetic urine, and pharmaceutical tablets ranged from 93.9% to 107.5%, indicating that there is no matrix effect. Furthermore, an interference test was performed with several drugs did not show any significant changes in the ethinylestradiol analytical signal, guaranteeing a greater precision of the method. These results reinforce the possibility of applying the proposed method in loco with a practical and fast way, without the need to use significant amounts of sample.

Photoelectrocatalytic degradation of 17α-ethinylestradiol and estrone under UV and visible light using nanotubular oxide arrays grown on Ti-0.5wt%W.

Environmental concern with emerging contaminants has increased in recent years, especially with regard to endocrine-disrupting compounds (EDCs), among them hormones. Conventional water treatment processes have been shown to be ineffective in removing these compounds from water and sewage, while heterogeneous photocatalysis has been demonstrated to be a promising technique. However, the catalytic efficiency is strongly related to the choice of the photocatalyst material. In order to obtain a fast and efficient degradation of these endocrine disruptors, nanotubes grown on Ti-0.5wt%W alloy (NT/Ti-0.5W) were used in photocatalytic (PC) and photoelectrocatalytic (PEC) processes for the degradation of estrone (E1) and 17α-ethinylestradiol (EE2) under irradiation with ultraviolet (UV) and visible light. The NT/Ti-0.5W catalysts were synthesized by an anodization process, followed by thermal treatment at 450 °C. Raman, X-ray diffraction and diffuse reflectance spectroscopic analyses indicated that the tungsten doping process had modified the nanotubular TiO2. The doped samples exhibited superior photoactivity compared to un-doped samples and other semiconductors under UV and visible irradiation due to a reduction in the rate of recombination of photogenerated charges and the displacement of the flat-band potential to more negative values. Higher values of the degradation rate constant were found for both hormones in the PEC process using NT/Ti-0.5W under UV radiation; the percentage removals of EE2 and E1 were 66% and 53.4%, respectively, after only 2 min of treatment. With visible light, 1.8 min and 4.6 h were required for the removal of 50% of E1 and EE2, respectively. The degradation of E1 could be fit with a zero-order kinetic model, while a first-order kinetic model was required for EE2 degradation. Degradation routes were suggested for E1 and EE2. The results demonstrate that the combined use of NT/Ti-0.5W and the PEC process provides excellent performance for the degradation of emerging contaminants in wastewater when compared to a NT/TiO2 electrode.

Assessing the impact of synthetic estrogen on the microbiome of aerated submerged fixed-film reactors simulating tertiary sewage treatment and isolation of estrogen-degrading consortium.

17α-ethinylestradiol (EE2) is a synthetic estrogen that can cause harmful effects on animals, such as male feminization and infertility. However, the impact of the EE2 contamination on microbial communities and the potential role of bacterial strains as bioremediation agents are underexplored. The aim of this work was to evaluate the impact of EE2 on the microbial community dynamics of aerated submerged fixed-film reactors (ASFFR) simulating a polishing step downstream of a secondary sewage treatment. For this purpose, the reactors were fed with a synthetic medium with low COD content (around 50 mg l-1), supplemented (reactor H) or not (reactor C) with 1 µg l-1 of EE2. Sludge samples were periodically collected during the bioreactors operation to assess the bacterial profile over time by 16S rRNA gene amplicon sequencing or by bacterial isolation using culture-dependent approach. The results revealed that the most abundant phyla in both reactors were Proteobacteria and Bacteroidetes. At genus level, Chitinophagaceae, Nitrosomonas and Bdellovibrio predominated. Significant effects caused by EE2 treatment and bioreactors operating time were observed by non-metric multidimensional scaling. Therefore, even at low concentrations as 1 µg l-1, EE2 is capable of influencing the bioreactor microbiome. Culture-dependent methods showed that six bacterial isolates, closely related to Pseudomonas and Acinetobacter genera, could grow on EE2 as the sole carbon source under aerobic conditions. These organisms may potentially be used for the assembly of an EE2-degrading bacterial consortium and further exploited for bioremediation applications, including tertiary sewage treatment to remove hormone-related compounds not metabolized in secondary depuration stages.

Ethinylestradiol and its effects on the macrophages in the prostate of adult and senile gerbils.

Prenatal and neonatal exposure to estrogenic compounds, such as ethinylestradiol (EE), promotes a variety of developmental disorders, including malformations and alterations in the morphology of glands, such as the prostate gland. Therefore, the aim of this study was to evaluate the morphological effects of neonatal exposure to EE on prostatic tissue and on the identification and quantification of gerbil gland macrophages in adult and senile Mongolian gerbils. The animals were exposed to EE (10 µg/kg/day) and to the vehicle, mineral oil (100 µL) (control group) during the first 10 days of postnatal life (lactation period). Adult gerbils were euthanized at 120 days and senile gerbils at 12 months of age. Our findings permitted verification of the presence of areas with proliferative foci in the prostate glandular portions in the adult and senile animals exposed to EE. There was also an increase in macrophages in the prostate tissue of adult and senile gerbils; these cell types alter the stromal microenvironment and possibly modify the interactions between the epithelium and stroma. Neonatal exposure to EE changes the pattern of prostatic development, leading to alterations in the arrangement of cells, including macrophages, and may be related to the onset of proliferative disorders in the prostate of adult gerbils and during aging.

Determination of 17α-ethinylestradiol and toxic metals in surface waters, and estimation of daily intake.

The presence of substances such as hormones and toxic metal in aquatic ecosystem is interesting to the scientific community due to their adverse effects. We quantified 17α-ethynylestradiol (EE2) and toxic metals in the surface waters from Sorocaba and Pirajibu Rivers, in São Paulo State, and we estimated the daily intake for hormone, based on the amount of water consumed. EE2, Cd, Hg, As, Pb, and Mn were seasonally quantified in six different locations along the rivers. EE2 was evaluated by high-performance liquid chromatography. Toxic metals were determined by inductively coupled plasma mass spectrometer. Considering the entire sample year, EE2 concentrations ranged from 4.5 to 48.2 µg L-1. Comparing Sorocaba and Pirajibu rivers, the sample point in the entrance of the Pirajibu River through the city of Itu, São Paulo State, had higher amounts of EE2. Regarding metals, all results are according to the Brazilian and World Health Organization guidelines for drinking-water quality, except for Mn levels, which were higher than the limits in Autumn season in two locations. The estimated daily intake ranged from 13.45 to 40.9 µg/day/person. In conclusion, concentrations of EE2 in the Sorocaba and Pirajibu Rivers were higher than in other countries. The levels were as high as an intake of one pill for each person every day (considering an oral contraceptive has 0.03 mg of ethinylestradiol). Even though concentrations of toxic elements are in accordance with the Brazilian Regulation and World Health Organization, legislation for hormones and drugs needs to advance.

Semi-synthesis of ß-keto-1,2,3-triazole derivatives from ethinylestradiol and evaluation of the cytotoxic activity.

In this study, we report our contribution to the application of the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction for the synthesis of ß-keto-1,2,3-triazole derivatives 3a-f from ethinylestradiol and their application in the inhibition of two human cancer cells lines: human breast adenocarcinoma (MCF-7) and human hepatocellular carcinoma (HepG2). The ß-keto-1,2,3-triazole derivates 3a-f exhibited moderate cytotoxic activity for the HepG2 cells with IC50 values of 29.7 µM (3a), 16.4 µM (3b), 17.8 µM (3c), 20.4 µM (3d), 28.1 µM (3e) and 28.2 µM (3f). The semi-synthetic ß-keto-1,2,3-triazoles derivatives 3a-f were all characterized by FT-IR, NMR, HRMS and [α]D.

Estrogen levels in surface sediments from a multi-impacted Brazilian estuarine system.

Estrogen levels were assessed in surface sediments from one of the most industrialized and urbanized estuarine systems in Latin America (SSES, Santos and São Vicente estuarine system). Estriol (E3) presented quantifiable levels in all sampled sites, ranging from 20.9 ng g-1 to 694.2 ng g-1. 17ß-estradiol (E2) and 17α-ethinylestradiol (EE2) were also detected in almost all sampled sites. The highest concentration of E2 was 23.9 ng g-1, whereas high levels of EE2 86.3 ng g-1. The occurrence of estrogens in SSES was diffuse and partially related to a domestic sewage outfall. Estrogens were also found in areas with substantial contribution of sanitary effluents from domiciles not covered by sanitation services. Our results reinforce that studies on environmental contamination by estrogens should not be spatially limited to the vicinities of point sources. These results contribute to raise awareness on the need of a formal approach to assess ecological risks of estrogens in the SSES.

Celastrol Attenuates Intrahepatic Cholestasis of Pregnancy by Inhibiting Matrix Metalloproteinases-2 and 9.

INTRODUCTION AND AIM: Matrix metalloproteinase (MMP)-2 and MMP-9 are reported to participate in several pregnancy-related diseases, including intrahepatic cholestasis of pregnancy (ICP), which is a severe liver disorder in pregnant women. Meanwhile, ample evidences have demonstrated that celastrol inhibits the activity and expression of MMPs. The present study aims to examine the effect of celastrol to alleviate symptoms of ICP in rat model. MATERIAL AND METHODS: By inducing ICP with 17 - ethinylestradiol in pregnant female rats, we assessed the impact of celastrol administration on symptoms of ICP, such as the rate of bile flow, the level of total bile acids (TBA), and the activities of MMP-2 and -9. Furthermore, the correlations between the levels of MMPs with the examined ICP symptoms were investigated. RESULTS: In rats with ICP, both MMP-2 and -9 exhibited significantly elevated activities, which were inhibited by the administration of celastrol. Furthermore, ICP symptoms such as bile flow rate and total TBA were restored by celastrol. Lastly, there were strong correlations between levels of the two MMPs and TBA. CONCLUSION: Our findings described for the first time the effects of celastrol to attenuate ICP symptoms through an inhibition of both MMP-2 and -9, providing evidence for a potential role of celastrol as a new drug for the treatment of ICP.

Stability of immobilized laccase on Luffa Cylindrica fibers and assessment of synthetic hormone degradation.

In this work were studied the pH, thermal, and storage stability of free and immobilized laccases. Enzymes were produced by Pleurotus ostreatus on potato dextrose (PD) broth and potato dextrose modified (PDM) broth, and immobilized using Luffa cylindrica fibers as support. Both free and immobilized enzymes were assessed on their respective enzymatic activities and for 17α-ethinylestradiol (EE2) degradation. The optimum pH conditions concerning laccase activity ranged from 3.6 to 4.6, while temperature ranged between 30 °C and 50 °C for both free and immobilized enzyme. Laccase produced using PD broth presented greater storage stability and thermal stability than that of PDM. Best EE2 removals were of 79.22% and 75.00% for the free and immobilized enzymes, respectively. Removal rates were assessed during 8 h at pH 5. The removal of 17α-ethinylestradiol was stabilized in the fourth cycle of use. Results imply that immobilization promoted stability towards pH and temperature variations, although media played a decisive role in the enzymatic activity. Both free and immobilized laccases of P. ostreatus were able to degrade EE2, whereas immobilized laccase in PDM medium presented possible reuse applicability, albeit removal was not optimal when compared to other reports.

Association between hormonal contraception and injuries induced by human papillomavirus in the uterine cervix / Associação entre a contracepção hormonal e lesões induzidas pelo vírus do papiloma humano no colo uterino

Abstract Objective To evaluate the association between hormonal contraception and the appearance of human papillomavirus HPV-induced lesions in the uterine cervix of patients assisted at a school outpatient clinic - ObGyn outpatient service of the Universidade do Sul de Santa Catarina. Methods A case-control study, with women in fertile age, performed between 2012 and 2015. A total of 101 patients with cervical lesions secondary to HPV were included in the case group, and 101 patients with normal oncotic colpocytology, in the control group. The data were analyzed through the Statistical Package for the Social Sciences (SPSS, IBM Corp. Armonk, NY, US) software, version 24.0, using the 95% confidence interval. To test the homogeneity of the proportions, the chi-square (χ2) test was used for the qualitative variables, and the Student t-test, for the quantitative variables. Results When comparing the occurrence of HPV lesions in users and non-users of combined oral contraceptives (COCs), the association with doses of 0.03 mg or higher of ethinylestradiol (EE) was observed. Thus, a higher probability of developing cervical lesions induced by HPV was identified (odds ratio [OR]: 1.9 p = 0.039); and when these cases were separated by the degree of the lesion, the probability of these patients presentingwith lowgrade squamous intraepithelial lesion was 2.1 times higher (p = 0.036), but with no impact on high-grade squamous intraepithelial lesions and the occurrence of invasive cancer. No significant differences were found in the other variables analyzed. Conclusion Although the results found in the present study suggest a higher probability of the users of combined hormonal contraceptives with a concentration higher than 0.03 mg of EE to develop low-grade intraepithelial lesions, more studies are needed to conclude causality.

Resumo Objetivo Avaliar a associação entre a contracepção hormonal e a presença de lesões induzidas pelo vírus do papiloma humano (HPV) no colo uterino de pacientes do serviço de ginecologia e obstetrícia do ambulatório de especialidade médicas da Universidadedo Sul de Santa Catarina - AME/UNISUL. Métodos Estudo observacional do tipo caso-controle, commulheres no menacme, no período compreendido entre 2012 e 2015. Foram incluídas 101 pacientes com lesões cervicais secundárias ao HPV, no grupo caso, e 101 pacientes com colpocitologia oncótica normal, no grupo controle. Os dados foram analisados por meio do programa SPSS 24.0, utilizando-se o intervalo de confiança de 95%. Para testar a homogeneidade de proporções foram utilizados o teste do qui-quadrado (χ2) para as variáveis qualitativas e o teste t de Student para as variáveis quantitativas. Resultados Ao comparar-se a ocorrência das lesões pelo HPV em usuárias de contraceptivos orais combinados (COCs) com a em não usuárias, observou-se a associação com doses de 0.03 mg ou superiores de etinilestradiol (EE), na qual se identificou 1.9 vezes mais probabilidade destas desenvolverem lesões cervicais induzidas pelo HPV (p = 0.039); ao separar-se esses casos pelo grau da lesão, a probabilidade destas pacientes apresentarem lesão cervical de baixo grau foi 2.1 vezes maior (p = 0.036), porémsemimpacto nas lesões cervicais de alto grau e na ocorrência de câncer invasor. Não foram encontradas diferenças significativas nas outras variáveis analisadas. Conclusão Embora os resultados encontrados no presente estudo sugiram maior probabilidade das usuárias de contraceptivo hormonal combinado, com concentração superior a 0.03 mg de EE, desenvolverem lesão cervical de baixo grau,mais estudos são necessários para concluir causalidade.