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1.
Cureus ; 16(6): e61980, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38983976

RESUMO

Most drug liver injury cases are the result of an unexpected interaction with medications. We present a 33-year-old woman, four months postpartum, on ethinyl estradiol/norgestrel, who presented in the ED with nausea, vomiting, abdominal pain, and severe pruritus six weeks after starting glecaprevir-pibrentasvir (GP) treatment. The patient was suspected to have a drug-induced liver injury (DILI), and GP was discontinued. Other potential causes of liver injury were ruled out via labs, imaging, and liver biopsy. The patient's liver function significantly improved after discontinuing GP. Few cases of DILI secondary to GP have been reported. However, to the best of our knowledge, DILI from the interaction of ethinyl estradiol and GP does not exist in published literature. In our case, DILI was likely due to the effect of GP and ethinyl estradiol on the liver's cytochrome 450 (CYP 450) system. The aim of this report is to raise awareness and improve pharmacovigilance, especially in patients receiving medications that are metabolized by the liver's CYP 450 system. Early detection of DILI secondary to drug-interaction and discontinuation of the culprit medication is the mainstay of treatment. However, there is a lack of evidence-based management strategies for premature discontinuation of GP in the setting of DILI while treating chronic hepatitis C virus (HCV) infection. Further investigations are warranted.

2.
Front Ophthalmol (Lausanne) ; 4: 1331298, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38984123

RESUMO

Introduction: Estrogen has emerged as a multifaceted signaling molecule in the retina, playing an important role in neural development and providing neuroprotection in adults. It interacts with two receptor types: classical estrogen receptors (ERs) alpha and beta, and G protein-coupled estrogen receptor (Gper). Gper differs from classical ERs in structure, localization, and signaling. Here we provide the first report of the temporal and spatial properties of Gper transcript and protein expression in the developing and mature mouse retina. Methods: We applied qRT-PCR to determine Gper transcript expression in wild type mouse retina from P0-P21. Immunohistochemistry and Western blot were used to determine Gper protein expression and localization at the same time points. Results: Gper expression showed a 6-fold increase during postnatal development, peaking at P14. Relative total Gper expression exhibited a significant decrease during retinal development, although variations emerged in the timing of changes among different forms of the protein. Gper immunoreactivity was seen in retinal ganglion cells (RGCs) throughout development and also in somas in the position of horizontal cells at early time points. Immunoreactivity was observed in the cytoplasm and Golgi at all time points, in the nucleus at early time points, and in RGC axons as the retina matured. Discussion: In conclusion, our study illuminates the spatial and temporal expression patterns of Gper in the developing mouse retina and provides a vital foundation for further investigations into the role of Gper in retinal development and degeneration.

3.
Endocrinology ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38984714

RESUMO

The blood-brain barrier (BBB) is an extensive capillary network that protects the brain from environmental and metabolic toxins while limiting drug delivery to the central nervous system (CNS). The ATP-Binding Cassette (ABC) transporter Breast cancer resistance protein (Bcrp) reduces drug delivery across the BBB by actively transporting its clinical substrates back into peripheral circulation before their entry into the CNS compartment. 17ß-estradiol (E2)-elicited changes in Bcrp transport activity and expression have been documented previously. We report a novel signaling mechanism by which E2 decreases Bcrp transport activity in mouse brain capillaries (MBCs) via rapid non-genomic signaling through estrogen receptor α (ERα). We extended this finding to investigate the effects of different endocrine-disrupting compounds (EDCs) and selective estrogen receptor modulators (SERMs) on Bcrp transport function. We also demonstrate sex-dependent expression of Bcrp and E2-sensitive Bcrp transport activity at the BBB ex vivo. This work establishes an explanted tissue-based model by which to interrogate EDCs and SERMs as modulators of nongenomic estrogenic signaling with implications for sex and hormonal regulation of therapeutic delivery into the CNS.

4.
Gynecol Endocrinol ; 40(1): 2375577, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38976762

RESUMO

Objective: To assess the safety and tolerability of ultra-low dose estradiol and dydrogesterone (E0.5 mg/D2.5 mg) among postmenopausal women. Methods: This pooled analysis of data from three clinical studies assessed the effects of continuous combined ultra-low-dose estradiol and dydrogesterone among postmenopausal women. Participants received E0.5 mg/D2.5 mg or placebo for 13 weeks (double-blind, randomized, European study), E0.5 mg/D2.5 mg or placebo for 12 weeks (double-blind, randomized, Chinese study), or E0.5 mg/D2.5 mg for 52 weeks (open-label, European study). Safety outcomes included treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), treatment discontinuation due to a TEAE, and adverse events of special interest (AESIs). Results: Overall, 1027 women were included in the pooled analysis (E0.5 mg/D2.5 mg, n = 736; placebo, n = 291). Mean treatment exposure was 288.9 days in the E0.5 mg/D2.5 mg group and 86.6 days in the placebo group. The proportion of women experiencing ≥1 TEAE was similar in the E0.5 mg/D2.5 mg and placebo groups (50.1% vs 49.5%, respectively). TESAEs occurred in 12 (1.6%) women receiving E0.5 mg/D2.5 mg and 9 (3.1%) women receiving placebo. Discontinuation of study treatment was infrequent in both groups (E0.5 mg/D2.5 mg: 1.5%; placebo: 2.4%). The occurrence of breast pain was more common in the E0.5 mg/D2.5 mg group than in the placebo group (2.0% vs 0.3%) as was uterine hemorrhage (6.5% vs 2.4%). The incidence of acne, hypertrichoses and weight increased was similar between groups. Conclusions: Across three studies, ultra-low-dose estradiol plus dydrogesterone was well tolerated among postmenopausal women, with no increase in TEAEs or TESAEs compared with placebo.


Assuntos
Didrogesterona , Estradiol , Pós-Menopausa , Humanos , Didrogesterona/administração & dosagem , Didrogesterona/efeitos adversos , Feminino , Estradiol/administração & dosagem , Estradiol/efeitos adversos , Pessoa de Meia-Idade , Método Duplo-Cego , Idoso , Terapia de Reposição de Estrogênios/métodos , Terapia de Reposição de Estrogênios/efeitos adversos , Progestinas/administração & dosagem , Progestinas/efeitos adversos , Fogachos/tratamento farmacológico
5.
Am J Obstet Gynecol ; 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38955323

RESUMO

BACKGROUND: Elagolix, an approved oral treatment for endometriosis-associated pain, has been associated with hypoestrogenic effects when used as monotherapy. Hormonal add-back therapy has the potential to mitigate these effects. OBJECTIVE: To evaluate efficacy, tolerability, and bone density outcomes of elagolix 200 mg twice daily with 1 mg estradiol /0.5 mg norethindrone acetate (add-back) therapy once daily compared with placebo in premenopausal women with moderate-to-severe endometriosis-associated pain. STUDY DESIGN: This ongoing, 48-month, phase 3 study consists of a 12-month, double-blind period, with randomization 4:1:2 to elagolix 200 mg twice daily with add-back therapy, elagolix 200 mg twice daily monotherapy for 6 months followed by elagolix with add-back therapy, or placebo. The co-primary endpoints were proportion of patients with clinical improvement (termed "responders") in dysmenorrhea and nonmenstrual pelvic pain at month 6. We report 12-month results on efficacy of elagolix with add-back therapy versus placebo in reducing dysmenorrhea, nonmenstrual pelvic pain, dyspareunia, and fatigue. Tolerability assessments include adverse events and change from baseline in bone mineral density. RESULTS: A total of 679 patients were randomized to elagolix with add-back therapy (n=389), elagolix monotherapy (n=97), or placebo (n=193). Compared with patients randomized to placebo, a significantly greater proportion of patients randomized to elagolix with add-back therapy responded with clinical improvement in dysmenorrhea (62.8% versus 23.7%; P≤.001) and nonmenstrual pelvic pain (51.3% versus 36.8%; P≤.001) at 6 months. Compared with placebo, elagolix with add-back therapy produced significantly greater improvement from baseline in 7 hierarchically ranked secondary endpoints including dysmenorrhea (months 12, 6, 3), nonmenstrual pelvic pain (months 12, 6, 3), and fatigue (months 6) (all P<.01). Overall, the incidence of adverse events was 73.8% with elagolix plus add-back therapy and 66.8% with placebo. The rate of severe and serious adverse events did not meaningfully differ between treatment groups. Study drug discontinuations associated with adverse events were low in patients receiving elagolix with add-back therapy (12.6%) and those receiving placebo (9.8%). Patients randomized to elagolix monotherapy exhibited decreases from baseline in bone mineral density of -2.43% (lumbar spine), -1.54% (total hip), and -1.78% (femoral neck) at month 6. When add-back therapy was added to elagolix at month 6, the change from baseline in bone mineral density remained in a similar range of -1.58% to -1.83% at month 12. However, patients who received elagolix plus add-back therapy from baseline exhibited little change from baseline in bone mineral density (<1% change) at months 6 and 12. CONCLUSION: Compared with placebo, elagolix with add-back therapy resulted in significant, clinically meaningful improvement in dysmenorrhea, nonmenstrual pelvic pain, and fatigue at 6 months that continued until month 12 for both dysmenorrhea and nonmenstrual pelvic pain. Elagolix with add-back therapy was generally well tolerated. Loss of bone mineral density at 12 months was greater in patients who received elagolix with add-back therapy than those who received placebo. However, the change in bone mineral density with elagolix plus add-back therapy was < 1% and was attenuated compared with bone loss observed with elagolix monotherapy.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38957997

RESUMO

Objective: Sex differences exist in sepsis, but the commitment of neutrophils to these differences remains unclear. Neutrophil extracellular traps (NETs) function to remove pathogens, yet excessive NETs release can contribute to organ damage. This study explores effects of the gender hormones on endotoxin-induced NETs using neutrophils from both male and female sources. Methods: Blood samples were collected from healthy volunteers. Isolated neutrophils were seeded in collagen-coated cell culture plates, and NETs were induced by lipopolysaccharide (LPS) treatment. After 15 minutes of LPS treatment, 17ß-estradiol (0.03-272.4 ng/mL), testosterone enanthate (0.01-10 ng/mL), dimethyl sulfoxide, or ethanol (vehicle control) was added to the plates. These were incubated for three hours at 37°C with 5% CO2. Neutrophil extracellular traps formation was assessed using immunofluorescence staining. Results: Lipopolysaccharide-induced NETs formation was significantly greater in females than in males. In male-derived neutrophils, 17ß-estradiol at above the blood concentrations significantly suppressed LPS-induced NETs. No effect was seen while using testosterone enanthate to NETs at any concentration. In female-derived neutrophils, 17ß-estradiol, which was near to the highest concentration of non-pregnant women's blood, tended to increase NETs. Testosterone enanthate, which was near to female blood concentration, significantly promoted NETs. Conclusions: Sex differences existed in LPS-induced NETs of human neutrophil. In males, high concentrations of 17ß-estradiol administration may have a suppressive effect on excessive NETs during infection. In females, endogenous gender hormones may promote NETs during infection. Sex differences in neutrophils may need to be considered in organ damage owing to NETs excess such as sepsis.

7.
Alzheimers Dement ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38948946

RESUMO

INTRODUCTION: Although reproductive hormones are implicated in cerebral small vessel disease in women, few studies consider measured hormones in relation to white matter hyperintensity volume (WMHV), a key indicator of cerebral small vessel disease. Even fewer studies consider estrone (E1), the primary postmenopausal estrogen, or follicle-stimulating hormone (FSH), an indicator of ovarian age. We tested associations of estradiol (E2), E1, and FSH to WMHV among women. METHODS: Two hundred twenty-two women (mean age = 59) underwent hormone assays (E1, E2, FSH) and 3T brain magnetic resonance imaging. Associations of hormones to WMHV were tested with linear regression. RESULTS: Higher E2 (B[standard error (SE)] = -0.17[0.06], P = 0.008) and E1 (B[SE] = -0.26[0.10], P = 0.007) were associated with lower whole-brain WMHV, and higher FSH (B[SE] = 0.26[0.07], P = 0.0005) with greater WMHV (covariates age, race, education). When additionally controlling for cardiovascular disease risk factors, associations of E1 and FSH to WMHV remained. DISCUSSION: Reproductive hormones, particularly E1 and FSH, are important to women's cerebrovascular health. HIGHLIGHTS: Despite widespread belief that sex hormones are important to women's brain health, little work has considered how these hormones in women relate to white matter hyperintensities (WMH), a major indicator of cerebral small vessel disease. We considered relations of estradiol (E2), estrone (E1), and follicle-stimulating hormone (FSH) to WMH in midlife women. Higher E2 and E1 were associated with lower whole-brain WMH volume (WMHV), and higher FSH with higher whole-brain WMHV. Associations of E1 and FSH, but not E2, to WMHV persisted with adjustment for cardiovascular disease risk factors. Findings underscore the importance of E2 and FSH to women's cerebrovascular health.

8.
Biomed Pharmacother ; 177: 117069, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38968802

RESUMO

The high mortality rate due to chemoresistance in patients with high-grade ovarian cancer (HGSOC) emphasizes the urgent need to determine optimal treatment strategies for advanced and recurrent cases. Our study investigates the interplay between estrogens and chemoresistance in HGSOC and shows clear differences between platinum-sensitive and -resistant tumors. Through comprehensive transcriptome analyzes, we uncover differences in the expression of genes of estrogen biosynthesis, metabolism, transport and action underlying platinum resistance in different tissues of HGSOC subtypes and in six HGSOC cell lines. Furthermore, we identify genes involved in estrogen biosynthesis and metabolism as prognostic biomarkers for HGSOC. Additionally, our study elucidates different patterns of estrogen formation/metabolism and their effects on cell proliferation between six HGSOC cell lines with different platinum sensitivity. These results emphasize the dynamic interplay between estrogens and HGSOC chemoresistance. In particular, targeting the activity of steroid sulfatase (STS) proves to be a promising therapeutic approach with potential efficacy in limiting estrogen-driven cell proliferation. Our study reveals potential prognostic markers as well as identifies novel therapeutic targets that show promise for overcoming resistance and improving treatment outcomes in HGSOC.

9.
J Eat Disord ; 12(1): 92, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956654

RESUMO

BACKGROUND: Plasma lipid concentrations in patients with anorexia nervosa (AN) seem to be altered. METHODS: We conducted a naturalistic study with 75 adult female patients with AN and 26 healthy female controls (HC). We measured plasma lipid profile, sex hormones and used self-report questionnaires at admission and discharge. RESULTS: Total cholesterol (median (IQR): 4.9 (1.2)) and triglycerides (TG) (1.2 (0.8)) were elevated in AN at admission (BMI 15.3 (3.4)) compared with HC (4.3 (0.7), p = 0.003 and 0.9 (0.3), p = 0.006) and remained elevated at discharge (BMI 18.9 (2.9)) after weight restoration treatment. Estradiol (0.05 (0.1)) and testosterone (0.5 (0.7)) were lower in AN compared with HC (0.3 (0.3), p = < 0.001 and 0.8 (0.5), p = 0.03) and remained low at discharge. There was no change in eating disorder symptoms. Depression symptoms decreased (33 (17) to 30.5 (19), (p = 0.007)). Regression analyses showed that illness duration was a predictor of TG, age was a predictor of total cholesterol and LDL, while educational attainment predicted LDL and TG. CONCLUSION: Lipid concentrations remained elevated following weight restoration treatment, suggesting an underlying, premorbid dysregulation in the lipid metabolism in AN that persists following weight restoration. Elevated lipid concentrations may be present prior to illness onset in AN. LEVEL OF EVIDENCE: III: Evidence obtained from well-designed cohort or case-control analytic studies.


Fat is essential for the human body. Too much fat in the blood can be a sign of underlying illness including heart disease. This study investigated how plasma lipids (fats) are affected in individuals with anorexia nervosa (AN). We included 75 adult female individuals with AN and 26 healthy female controls, and measured lipids, sex hormones, and used questionnaires upon admission and discharge from treatment. We found that low-weight individuals with AN had higher lipids than the healthy controls, and these lipids remained elevated after weight restoration treatment. Additionally, individuals with AN had lower levels of sex hormones (estradiol and testosterone) at their low weight, and they stayed low even after weight restoration treatment. Eating disorder symptoms remained unchanged, but depression symptoms decreased during treatment. In conclusion, the study suggests that individuals with AN have changes in their lipid metabolism, which persists even after weight restoration treatment. We don't know the reason behind these elevated lipids, and therefore, this should be investigated further in future study.

10.
J Endocr Soc ; 8(8): bvae108, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38962490

RESUMO

Background: A goal of gender-affirming hormone therapy (GAHT) for transgender women is to use estradiol to suppress endogenous production of testosterone. However, the effects of different estradiol regimens and route of administration on testosterone suppression is unknown. This is the first open-label randomized trial comparing different GAHT regimens for optimal estradiol route and dosing. Objective: To evaluate 1 month and 6 months testosterone suppression <50 ng/dL with pulsed (once- or twice-daily sublingual 17-beta estradiol) and continuous (transdermal 17-beta estradiol) GAHT. Methods: This study was conducted at an outpatient adult transgender clinic. Thirty-nine transgender women undergoing initiation of GAHT were randomly assigned to receive either once-daily sublingual, twice-daily sublingual, or transdermal 17-beta estradiol. All participants received spironolactone as an antiandrogen. Doses were titrated at monthly intervals to achieve total testosterone suppression <50 ng/dL. Results: Transdermal 17-beta estradiol resulted in more rapid suppression of total testosterone, lower estrone levels, with no differences in estradiol levels when compared to once-daily and twice-daily sublingual estradiol. Moreover, there was no difference in the mean estradiol dose between the once-daily and twice-daily sublingual 17-beta estradiol group. Conclusion: Continuous exposure with transdermal 17-beta estradiol suppressed testosterone production more effectively and with lower overall estradiol doses relative to once or twice daily sublingual estradiol. Most transgender women achieved cisgender women testosterone levels within 2 months on 1 or 2 0.1 mg/24 hours estradiol patches. Given no difference between once- or twice-daily sublingual estradiol, pulsed 17-beta estradiol likely provides no benefit for testosterone suppression.

11.
Mol Cell Endocrinol ; 592: 112325, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38968968

RESUMO

Polymetabolic syndrome achieved pandemic proportions and dramatically influenced public health systems functioning worldwide. Chronic vascular complications are the major contributors to increased morbidity, disability, and mortality rates in diabetes patients. Nitric oxide (NO) is among the most important vascular bed function regulators. However, NO homeostasis is significantly deranged in pathological conditions. Additionally, different hormones directly or indirectly affect NO production and activity and subsequently act on vascular physiology. In this paper, we summarize the recent literature data related to the effects of insulin, estradiol, insulin-like growth factor-1, ghrelin, angiotensin II and irisin on the NO regulation in physiological and diabetes circumstances.

12.
Pharmacol Res Perspect ; 12(4): e1234, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38961539

RESUMO

The association of hormonal contraception with increased risk of inflammatory bowel disease (IBD) observed in females suggests involvement of ovarian hormones, such as estradiol, and the estrogen receptors in the progression of intestinal inflammation. Here, we investigated the effects of prophylactic SERM2 and estradiol supplementation in dextran sulfate sodium-induced colitis using mice with intact ovaries and ovariectomized (OVX) female mice. We found that graded colitis score was threefold reduced in the OVX mice, compared to mice with intact ovaries. Estradiol supplementation, however, aggravated the colitis in OVX mice, increasing the colitis score to a similar level than what was observed in the intact mice. Further, we observed that immune infiltration and gene expression of inflammatory interleukins Il1b, Il6, and Il17a were up to 200-fold increased in estradiol supplemented OVX colitis mice, while a mild but consistent decrease was observed by SERM2 treatment in intact animals. Additionally, cyclo-oxygenase 2 induction was increased in the colon of colitis mice, in correlation with increased serum estradiol levels. Measured antagonist properties of SERM2, together with the other results presented here, indicates an exaggerating role of ERα signaling in colitis. Our results contribute to the knowledge of ovarian hormone effects in colitis and encourage further research on the potential use of ER antagonists in the colon, in order to alleviate inflammation.


Assuntos
Colite , Sulfato de Dextrana , Estradiol , Receptor alfa de Estrogênio , Ovariectomia , Animais , Feminino , Receptor alfa de Estrogênio/metabolismo , Colite/induzido quimicamente , Colite/metabolismo , Colite/tratamento farmacológico , Camundongos , Estradiol/farmacologia , Estradiol/sangue , Camundongos Endogâmicos C57BL , Estrogênios/farmacologia , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Interleucina-17/metabolismo , Colo/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , Interleucina-6/metabolismo , Interleucina-1beta/metabolismo
13.
J Chromatogr A ; 1730: 465138, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38970874

RESUMO

In this study, an enhanced selective recognition strategy was employed to construct a novel solid-phase microextraction fiber coating for the detection of 17ß-estradiol, characterized by the combination of aptamer biorecognition and molecularly imprinted polymer recognition. Benefiting from the combination of molecularly imprinted and aptamer, aptamer-molecularly imprinted (Apt-MIP) fiber coating had synergistic recognition effect. The effects of pH, ion concentration, extraction time, desorption time and desorption solvent on the adsorption capacity of Apt-MIP were investigated. The adsorption of 17ß-estradiol on Apt-MIP followed pseudo-second order kinetic model, and the Freundlich isotherm. The process was exothermic and thermodynamically spontaneous. Compared with polymers that only rely on imprinted recognition, non-imprinted recognition or aptamer affinity, Apt-MIP had the best recognition performance, which was 1.30-2.20 times that of these three materials. Furthermore, the adsorption capacity of Apt-MIP for 17ß-estradiol was 885.36-1487.52 times than that of polyacrylate and polydimethylsiloxane/divinylbenzone commercial fiber coatings. Apt-MIP fiber coating had good stability and could be reused for more than 15 times. Apt-MIP solid-phase microextraction coupled with high-performance liquid chromatography was successfully applied to the determination of 17ß-estradiol in pork, chicken, fish and shrimp samples, with satisfactory recoveries of 79.61 %-105.70 % and low limits of detection (0.03 µg/kg). This work provides new perspectives and strategies for sample pretreatment techniques based on molecular imprinting technology and improves analytical performance.

14.
Arch. cardiol. Méx ; 94(2): 127-132, Apr.-Jun. 2024. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1556908

RESUMO

Abstract Objective: Analyze sex hormone's influence during Chagas disease. Methods: Male and female BALB/c mice were divided into six groups, four experimental (sham, orchiectomized, orchiectomized and supplemented with estradiol, orchiectomized supplemented with testosterone, oophorectomized, oophorectomized and supplemented with estradiol, and oophorectomized and supplemented with testosterone), and two control (healthy and intraperitoneally with T. cruzi strain NINOA infected). Clinical data were recorded daily, parasitemia was evaluated using a Neubauer chamber during the infection, and heart histopathological analysis was performed using the paraffin embedding technique. To analyze parasitemia curves and the area under the parametric curves, two-way ANOVA test was performed to correlate groups' data. P-values < 0.05 were considered statistically significant. Results: Higher mortality rates, cardiomegaly, hepatomegaly, ascites, edema, higher parasitemia levels, more amastigote nests, and more severe inflammatory infiltrate were found in higher testosterone concentration mice, whereas in higher estradiol concentration groups, paresia, prostration, edema, and necrosis were found. Conclusions: Our results showed that testosterone increased infection severity, whereas estradiol had the opposite effect. This research improves the understanding of sex hormones´ infuence upon this infection to contribute with the handling of Chagas´ disease.


Resumen Objetivo: Analizar la influencia de las hormonas durante la enfermedad de Chagas. Métodos: Se separaron grupos de ratones macho y hembras BALB/c, todos infectados con T. cruzi (cepa NINOA), 4 grupos experimentales de machos (Sham, orquidectamizados, orquidectimezados y suplementados con estradiol, orquidectamizaos y suplementados con testosterona). 4 grupos experimentales de hembras (oforectomizadas, oforectomizadas y suplementadas con estradiol, oforectomizadas y suplementadas con testosterona y sham), and y dos grupos control para cada sexo (sin infección e infectados intraperitonealmente con T. cruzi (cepa NINOA). Los datos clínicos fueron registrados diariamente, la parasitemia fue evaluada durante toda la infección utilizando una cámara de Neubauer y el análisis histopatológico del corazón fue realizada con la técnica de inclusión en parafina. Para el análisis de las curvas de parasitemia y el área bajo la curva, se realizó una prueba de ANOVA de dos vías, p < 0.05 fueron considerados estadísticamente diferentes. Resultados: Las mayores tasas de mortalidad, cardiomegalia, hepatomegalia y mayor infiltrado inflamatorio, se encontró en los ratones con una mayor concentración de testosterona. En contraste los ratones con mayor concentración de estradiol presentaron paresia, postración edema y necrosis. Conclusiones: Nuestros resultados ponen en manifiesto que la testosterona incrementa la severidad del curso de la enfermedad de Chagas, mientras que el estradiol tuvo el efecto opuesto. Este trabajo mejora el entendimiento del rol que juegan las hormonas sexuales en esta infección para contribuir en un mejor manejo de la enfermedad de Chagas.

15.
Mikrochim Acta ; 191(7): 375, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849611

RESUMO

The production, optimisation, physicochemical, and electroanalytical characterisation of a low-cost electrically conductive additive manufacturing filament made with recycled poly(lactic acid) (rPLA), castor oil, carbon black, and graphite (CB-G/PLA) is reported. Through optimising the carbon black and graphite loading, the best ratio for conductivity, low material cost, and printability was found to be 60% carbon black to 40% graphite. The maximum composition within the rPLA with 10 wt% castor oil was found to be an overall nanocarbon loading of 35 wt% which produced a price of less than £0.01 per electrode whilst still offering excellent low-temperature flexibility and reproducible printing. The additive manufactured electrodes produced from this filament offered excellent electrochemical performance, with a heterogeneous electron (charge) transfer rate constant, k0 calculated to be (2.6 ± 0.1) × 10-3 cm s-1 compared to (0.46 ± 0.03) × 10-3 cm s-1 for the commercial PLA benchmark. The additive manufactured electrodes were applied to the determination of ß-estradiol, achieving a sensitivity of 400 nA µM-1, a limit of quantification of 70 nM, and a limit of detection of 21 nM, which compared excellently to other reports in the literature. The system was then applied to the detection of ß-estradiol within four real water samples, including tap, bottled, river, and lake water, where recoveries between 95 and 109% were obtained. Due to the ability to create high-performance filament at a low material cost (£0.06 per gram) and through the use of more sustainable materials such as recycled polymers, bio-based plasticisers, and naturally occurring graphite, additive manufacturing will have a permanent place within the electroanalysis arsenal in the future.

16.
Mikrochim Acta ; 191(7): 383, 2024 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-38861005

RESUMO

A competitive-type photoelectrochemical (PEC) aptasensor coupled with a novel Au@Cd:SnO2/SnS2 nanocomposite was designed for the detection of 17ß-estradiol (E2) in microfluidic devices. The designed Au@Cd:SnO2/SnS2 nanocomposites exhibit high photoelectrochemical activity owing to the good matching of cascade band-edge and the efficient separation of photo-generated e-/h+ pairs derived from the Cd-doped defects in the energy level. The Au@Cd:SnO2/SnS2 nanocomposites were loaded into carbon paste electrodes (CPEs) to immobilize complementary DNA (cDNA) and estradiol aptamer probe DNA (E2-Apt), forming a double-strand DNA structure on the CPE surface. As the target E2 interacts with the double-strand DNA, E2-Apt is sensitively released from the CPE, subsequently increasing the photocurrent intensity due to the reduced steric hindrance of the electrode surface. The competitive-type sensing mechanism, combined with high PEC activity of the Au@Cd:SnO2/SnS2 nanocomposites, contributed to the rapid and sensitive detection of E2 in a "signal on" manner. Under the optimized conditions, the PEC aptasensor exhibited a linear range from 1.0 × 10-13 mol L-1 to 3.2 × 10-6 mol L-1 and a detection limit of 1.2 × 10-14 mol L-1 (S/N = 3). Moreover, the integration of microfluidic device with smartphone controlled portable electrochemical workstation enables the on-site detection of E2. The small sample volume (10 µL) and short analysis time (40 min) demonstrated the great potential of this strategy for E2 detection in rat serum and river water. With these advantages, the PEC aptasensor can be utilized for point-of-care testing (POCT) in both clinical and environmental applications.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Técnicas Eletroquímicas , Estradiol , Ouro , Limite de Detecção , Nanocompostos , Sulfetos , Compostos de Estanho , Compostos de Estanho/química , Aptâmeros de Nucleotídeos/química , Nanocompostos/química , Ouro/química , Estradiol/análise , Estradiol/sangue , Estradiol/química , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/instrumentação , Sulfetos/química , Cádmio/química , Cádmio/análise , Processos Fotoquímicos , Dispositivos Lab-On-A-Chip
17.
Environ Pollut ; 356: 124333, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38848960

RESUMO

17ß-estradiol is a naturally occurring estrogen, and livestock manure applied to agricultural fields is a major source to the environment. Liquid swine manure is widely applied to agricultural fields in the Canadian Prairies, a region where the majority of the annual runoff occurs during a brief snowmelt period over frozen soil. Transport of estrogens from manure amendments to soil during this important hydrological period is not well understood but is critical to mitigating the snowmelt-driven offsite transport of estrogens. This study quantified the concentration and load of 17ß-estradiol in snowmelt from an agricultural field with a history of manure application under manure application methods: no manure applied, manure applied on the sub-surface, and on the surface, using a laboratory simulation study with flooded intact soil cores and a field study during snowmelt. A higher concentration of 17ß-estradiol was in the laboratory simulation than in the field (mean laboratory pore water = 1.65 ± 1.2 µg/L; mean laboratory flood water = 0.488 ± 0.58 µg/L; and mean field snowmelt = 0.0619 ± 0.048 µg/L). There were no significant differences among manure application methods for 17ß-estradiol concentration. Laboratory pore water concentrations significantly increased over time, corresponding with changes in pH. In contrast, there was no significant change in the field snowmelt concentrations of 17ß-estradiol over time. However, for both laboratory simulation experiments and field-based snowmelt experiments, mean concentrations of 17ß-estradiol were higher with subsurface than surface-applied manure, and the cumulative load of 17ß-estradiol was significantly higher in the sub-surface than in surface applied. The mean cumulative load from the field study across all treatments (6.91 ± 3.7 ng/m2) approximates the magnitude of 17ß-estradiol that could be mobilized from manured fields. The sub-surface application of manure seems to increase the persistence of 17ß-estradiol in soil, thus enhancing the potential loss to snowmelt runoff.

18.
Artigo em Inglês | MEDLINE | ID: mdl-38878133

RESUMO

PURPOSE: Alcohol is posited to affect sex steroid hormone concentrations, and a growing body of research has demonstrated menstrual cycle effects on women's use of alcohol. The present targeted review synthesizes the literature examining the relationship between alcohol use and estradiol in women and suggests directions for future research. METHODS: Articles were identified using the PubMed database using the following criteria: published in English, presented original findings for women, were peerreviewed, and included measures of estradiol levels in the analyses. Twenty-nine articles were identified for inclusion. RESULTS: Results from this review indicate acute alcohol use temporarily increases estradiol levels in women, and this may be strongest when gonadotropins are high. Regular alcohol use (≥1 drink per day) increases estradiol levels, but estradiol appears to be suppressed in women with alcohol use disorders and physiologic dependence. Alcohol use tends to be highest in women during ovulation, when estradiol is high, and progesterone is low. CONCLUSION: Alcohol use increases estradiol levels in women, particularly in the presence of gonadotropins. More research is needed to assess the effect of estradiol on alcohol use in women. Research on the relationship of estrogen and alcohol use in women is needed to elucidate health outcomes through the lifespan.

19.
Biofactors ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886986

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin-converting enzyme 2 (ACE2) on host cells, via its spike protein, and transmembrane protease, serine 2 (TMPRSS2) cleaves the spike-ACE2 complex to facilitate virus entry. As rate-limiting steps for virus entry, modulation of ACE2 and/or TMPRSS2 may decrease SARS-CoV-2 infectivity and COVID-19 severity. In silico modeling suggested the natural bioactive flavonoid quercetin can bind to ACE2 and a recent randomized clinical trial demonstrated that oral supplementation with quercetin increased COVID-19 recovery. A range of cultured human cells were assessed for co-expression of ACE2 and TMPRSS2. Immortalized Calu-3 lung cells, cultured and matured at an air-liquid interface (Calu-3-ALIs), were established as the most appropriate. Primary bronchial epithelial cells (PBECs) were obtained from healthy adult males (N = 6) and cultured under submerged conditions to corroborate the outcomes. Upon maturation or reaching 80% confluence, respectively, the Calu-3-ALIs and PBECs were treated with quercetin, and mRNA and protein expression were assessed by droplet digital PCR and ELISA, respectively. SARS-CoV-2 infectivity, and the effects of pre- and co-treatment with quercetin, was assessed by median tissue culture infectious dose assay. Quercetin dose-dependently decreased ACE2 and TMPRSS2 mRNA and protein in both Calu-3-ALIs and PBECs after 4 h, while TMPRSS2 remained suppressed in response to prolonged treatment with lower doses (twice daily for 3 days). Quercetin also acutely decreased ADAM17 mRNA, but not ACE, in Calu-3-ALIs, and this warrants further investigation. Calu-3-ALIs, but not PBECs, were successfully infected with SARS-CoV-2; however, quercetin had no antiviral effect, neither directly nor indirectly through downregulation of ACE2 and TMPRSS2. Calu-3-ALIs were reaffirmed to be an optimal cell model for research into the regulation of ACE2 and TMPRSS2, without the need for prior genetic modification, and will prove valuable in future coronavirus and respiratory infectious disease work. However, our data demonstrate that a significant decrease in the expression of ACE2 and TMPRSS2 by a promising prophylactic candidate may not translate to infection prevention.

20.
Eur J Obstet Gynecol Reprod Biol ; 299: 213-218, 2024 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-38897097

RESUMO

OBJECTIVE: To evaluate the use of oral nomegestrol acetate/estradiol in random start rapid preparation of endometrium before office hysteroscopic polypectomy. STUDY DESIGN: Multicenter, prospective, randomized controlled trial. SETTING: University hospitals. PARTICIPANTS: 80 adult women undergoing office hysteroscopic polypectomy between January 2023 and March 2024 were randomized to intervention (n = 40) or control (n = 40). Exclusion criteria included the presence of endouterine pathology other than endometrial polyps solely. METHODS: Subjects in the intervention group were treated with oral nomegestrol acetate/estradiol 1.5 mg/2.5 mg/day started taking the drug from an indefinite time in the menstrual cycle (random start) for 14 days. Subjects in the control group did not receive any pharmaceutical treatment and underwent polypectomy between days 8 and 11 of the menstrual cycle. RESULTS: On the day of the procedure, the difference in pre- and post-office hysteroscopic polypectomy endometrial ultrasound thickness was statistically significant between the two groups, with endometrial thickness in both measurements being thinner for the intervention group (p < 0.001). In the nomegestrol acetate/estradiol-treated group, compared with the control, there was also a statistically significant difference in the physician's assessment of the quality of endometrial preparation (p < 0.001), the quality of visualization of the uterine cavity (p < 0.001), and satisfaction with the performance of the procedure (p < 0.001). Finally, all surgical outcomes analyzed were better in the treatment group. CONCLUSION: Treatment with nomegestrol acetate/estradiol could provide rapid, satisfactory and low-cost preparation of the endometrium before office polypectomy, thus improving surgical performance and woman's compliance. TRIAL REGISTRATION: ClinicalTrials.gov NCT06316219.

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