Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.343
Filtrar
1.
Anal Chem ; 93(40): 13513-13519, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34596384

RESUMO

This paper demonstrates the hierarchical design of functional, fibrous polymer monoliths. The monoliths are composed of conjugated microporous polymers that not only are embedded with heteroatoms but also feature fibrous yet compressible structures due to the in situ self-assembly process that occurs during the polymerization process. Therefore, the doped nitrogen atoms can allow the growth of zeolitic imidazolate framework (ZIF) nanocrystals, which causes the homogeneous encapsulation of individual fibers. The resulting hybrid monoliths exhibit enhanced physical properties as well as catalytic activity, allowing the formation of an additional coating layer via a thiol-epoxy reaction. The deliberate inclusion of template molecules during the reaction forms molecularly imprinted sites on the fibers to afford functional monoliths. As a proof of concept, the hierarchically designed materials are able to show effective recognition properties toward diethylstilbestrol, an endocrine disruptor, taking advantage of the binding sites that selectively capture the analyte molecules and the fibrous morphology that increases the accessibility of these binding sites. We envisage that the incorporation of various heteroatoms or nanocrystals will bring about the bespoke design of advanced monoliths with autonomous functions, leading to smart textile systems.


Assuntos
Nanopartículas , Zeolitas , Dietilestilbestrol , Polimerização , Polímeros
2.
Environ Health ; 20(1): 96, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34452632

RESUMO

BACKGROUND: Endometriosis, which affects 10-15 % of women of reproductive age, is an estrogen-driven condition influenced by environmental and genetic factors. Exposition to estrogen-like endocrine-disrupting chemicals (EDCs) has been reported to contribute to the fetal origin of this disease. CASE PRESENTATION: We report here an informative family in which all prenatally DES-exposed daughters and subsequent granddaughters presented endometriosis, whereas the unexposed first daughter and her progeny presented no gynecological disorders. Moreover, the only post-pubertal great-granddaughter, who presents chronic dysmenorrhea that remains resistant to conventional therapy, is at risk of developing endometriosis. The mother (I-2) was prescribed DES (30 mg/day for 3 months) to inhibit lactation after each delivery. CONCLUSIONS: Although a direct causal link between the grandmother's treatment with DES and the development of endometriosis in possibly three exposed generations remains speculative, this report strengthens the suspicion that fetal exposition to DES contributes to the pathogenesis of adult diseases, such as endometriosis. It also highlights a multigenerational and likely transgenerational effect of EDCs.


Assuntos
Dietilestilbestrol/efeitos adversos , Dismenorreia/induzido quimicamente , Disruptores Endócrinos/efeitos adversos , Endometriose/induzido quimicamente , Estrogênios não Esteroides/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Feminino , Humanos , Gravidez
3.
Biomolecules ; 11(7)2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-34201983

RESUMO

Environmental estrogen is a substance that functions as an endocrine hormone in organisms and can cause endocrine system disruption. A typical environmental estrogen, diethylstilbestrol (DES), can affect normal sexual function and organism development. However, even though the effects of different exposure stages of DES on the endocrine system and gonadal development of zebrafish juveniles are unknown, sex determination is strongly influenced by endocrine-disrupting chemicals (EDCs). From 10-90 days post fertilization (dpf), juvenile zebrafish were exposed to DES (100 and 1000 ng/L) in three different stages (initial development stage (IDS), 10-25 dpf; gonadal differentiation stage (GDS), 25-45 dpf and gonadal maturity stage (GMS), 45-60 dpf). Compared with that of IDS and GMS, the growth indicators (body length, body weight, and others) decreased significantly at GDS, and the proportion of zebrafish females exposed to 100 ng/L DES was significantly higher (by 59.65%) than that of the control; in addition, the zebrafish were biased towards female differentiation. The GDS is a critical period for sex differentiation. Our results show that exposure to environmental estrogen during the critical gonadal differentiation period not only affects the development of zebrafish, but also affects the population development.


Assuntos
Dietilestilbestrol/toxicidade , Disruptores Endócrinos/toxicidade , Estrogênios não Esteroides/toxicidade , Gônadas/efeitos dos fármacos , Diferenciação Sexual/efeitos dos fármacos , Animais , Tamanho Corporal/efeitos dos fármacos , Tamanho Corporal/fisiologia , Feminino , Masculino , Diferenciação Sexual/fisiologia , Peixe-Zebra
4.
Int J Mol Sci ; 22(13)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34281152

RESUMO

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related mortality; thus, therapeutic targets continue to be developed. Anoctamin1 (ANO1), a novel drug target considered for the treatment of NSCLC, is a Ca2+-activated chloride channel (CaCC) overexpressed in various carcinomas. It plays an important role in the development of cancer; however, the role of ANO1 in NSCLC is unclear. In this study, diethylstilbestrol (DES) was identified as a selective ANO1 inhibitor using high-throughput screening. We found that DES inhibited yellow fluorescent protein (YFP) fluorescence reduction caused by ANO1 activation but did not inhibit cystic fibrosis transmembrane conductance regulator channel activity or P2Y activation-related cytosolic Ca2+ levels. Additionally, electrophysiological analyses showed that DES significantly reduced ANO1 channel activity, but it more potently reduced ANO1 protein levels. DES also inhibited the viability and migration of PC9 cells via the reduction in ANO1, phospho-ERK1/2, and phospho-EGFR levels. Moreover, DES induced apoptosis by increasing caspase-3 activity and PARP-1 cleavage in PC9 cells, but it did not affect the viability of hepatocytes. These results suggest that ANO1 is a crucial target in the treatment of NSCLC, and DES may be developed as a potential anti-NSCLC therapeutic agent.


Assuntos
Anoctamina-1/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Dietilestilbestrol/farmacologia , Proteínas de Neoplasias/antagonistas & inibidores , Anoctamina-1/metabolismo , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Dietilestilbestrol/metabolismo , Humanos , Neoplasias Pulmonares , Proteínas de Neoplasias/metabolismo , Transdução de Sinais
5.
Front Public Health ; 9: 674357, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34123993

RESUMO

Uterine leiomyoma (UL), common benign tumors in women of child-bearing age, are believed to be caused mainly by Qi stagnation and blood stasis, according to a theory of traditional Chinese medicine. Curcumae Rhizoma and Sparganii Rhizoma (CRSR) is a classical herb pair that activates blood circulation to dissipate blood stasis. The purpose of this study was to explore the prevention and treatment effects of CRSR component compatibility on UL in rats. We randomly assigned adult female non-pregnant rats into three groups: a normal control (NC) group, a UL model group, and a CRSR treatment group. We administered to the UL and CRSR groups oral gavage diethylstilbestrol and injected them with progesterone (P) to establish UL for 5 weeks. The CRSR group received a CRSR medicinal solution after daily modeling. The uterus morphology of the UL group showed significantly more swelling than did that of the NC group, and we found no significant abnormalities in the morphology of the CRSR group. The pathological changes associated with UL were relieved in the CRSR group. CRSR improved the related parameters of the uterus and ovarian coefficients, significantly reducing the concentrations of P in the serum and the concentrations of estradiol, P, estrogen receptor, and P receptor in the uterus and ovary. In addition, CRSR significantly improved the abnormal blood conditions of UL, shown by decreases in plasma viscosity, the erythrocyte sedimentation rate equation K value, and erythrocyte aggregation index. Therefore, CRSR component compatibility may prevent and cure UL through the above ways.


Assuntos
Leiomioma , Medicina Tradicional Chinesa , Animais , Dietilestilbestrol , Feminino , Leiomioma/tratamento farmacológico , Ratos , Rizoma , Útero
6.
Analyst ; 146(13): 4254-4260, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34100481

RESUMO

In this work, a novel electrochemiluminescence (ECL) aptasensor based on the resonance energy transfer (RET) effect between Ag3PO4-Cu-MOF (ii) and silver nanoparticles (Ag NPs) is proposed. The ECL emission spectra of Ag3PO4-Cu-MOF and the ultraviolet absorption spectra of Ag NPs showed a good spectral overlap. Based on this, we designed an "on-off-on" ECL sensing strategy for the sensitive and specific detection of diethylstilbestrol (DES). Under the optimal conditions, the linear range of the sensor for DES detection was 1.0 × 10-12-1.0 × 10-4 M, with a detection limit of 7.2 × 10-13 M (S/N = 3). The method showed simple and fast operation, high sensitivity and selectivity, a strong anti-interference ability and good stability. More importantly, the developed aptasensor exhibited excellent recognition towards residual DES in actual water samples. The sensor has superior measurement capability and potential application value in the field of environment water quality monitoring.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Dietilestilbestrol , Técnicas Eletroquímicas , Transferência de Energia , Limite de Detecção , Medições Luminescentes , Prata
7.
Artigo em Inglês | MEDLINE | ID: mdl-34052754

RESUMO

A novel fabric phase sorptive extraction protocol is developed for rapid exposure monitoring of six bisphenol analogues, including bisphenol A, bisphenol S, bisphenol F, bisphenol E, bisphenol B, bisphenol C, and diethylstilbestrol (DES) from human urine prior to high-performance liquid chromatography-photodiode array analysis. FPSE sample pretreatment protocol ensures the harmonization of the proposed method with the principles of Green Analytical Chemistry (GAC). Among eighteen evaluated FPSE membranes, sol-gel poly (ethylene glycol) (PEG) coated cellulose FPSE membrane resulted in the most efficient extraction. This polar FPSE membrane effectively exploits a number of advantageous features inherent to FPSE including sponge-like porous architecture of the sol-gel sorbent coating, favorable surface chemistry, flexibility and built-in permeability of cellulose fabric substrate, high primary contact surface area for rapid sorbent-analyte interaction, expanded pH, solvent and thermal stability as well as reusability of the FPSE membrane. Optimization was centered on the evaluation of critical parameters, namely the size of the FPSE membrane, the elution solvent mixture, the volume of the sample, the extraction time, the elution time, the kind of the external agitation mechanical stimulus, the ionic strength and the pH of the sample. The chromatographic separation was achieved on a Spherisorb C18 column and a gradient elution program with mobile phase consisted of 0.05 ammonium acetate solution and acetonitrile. The total analysis time was 17.4 min. The developed method was validated in terms of linearity, sensitivity, selectivity, precision, accuracy, stability, and ruggedness. The limits of detection and quantification varied from 0.26-0.62 ng/mL and 0.8-1.9 ng/mL, respectively. The relative recoveries were calculated between 90.6 and 108.8%, while the RSD values were <10% in all cases. The effectiveness of the proposed method was confirmed by its successful implementation in the bioanalysis of real urine samples.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Dietilestilbestrol/urina , Fenóis/urina , Feminino , Química Verde , Humanos , Limite de Detecção , Modelos Lineares , Masculino , Reprodutibilidade dos Testes , Têxteis
8.
Int J Mol Sci ; 22(8)2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33920546

RESUMO

Xenobiotic exposure during pregnancy and lactation has been linked to perinatal changes in male reproductive outcomes and other endocrine parameters. This pilot study wished to assess whether brief maternal exposure of rats to xenobiotics dibutyl phthalate (DBP) or diethylstilbestrol (DES) might also cause long-term changes in hypothalamic gene expression or in reproductive behavior of the resulting offspring. Time-mated female Sprague Dawley rats were given either DBP (500 mg/kg body weight, every second day from GD14.5 to PND6), DES (125 µg/kg body weight at GD14.5 and GD16.5 only), or vehicle (n = 8-12 per group) and mild endocrine disruption was confirmed by monitoring postnatal anogenital distance. Hypothalamic RNA from male and female offspring at PND10, PND24 and PND90 was analyzed by qRT-PCR for expression of aromatase, oxytocin, vasopressin, ER-alpha, ER-beta, kisspeptin, and GnRH genes. Reproductive behavior was monitored in male and female offspring from PND60 to PND90. Particularly, DES treatment led to significant changes in hypothalamic gene expression, which for the oxytocin gene was still evident at PND90, as well as in sexual behavior. In conclusion, maternal xenobiotic exposure may not only alter endocrine systems in offspring but, by impacting on brain development at a critical time, can have long-term effects on male or female sexual behavior.


Assuntos
Dibutilftalato/toxicidade , Dietilestilbestrol/toxicidade , Estrogênios não Esteroides/farmacologia , Hipotálamo/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Comportamento Sexual Animal , Animais , Aromatase/genética , Aromatase/metabolismo , Feminino , Hormônio Liberador de Gonadotropina/genética , Hormônio Liberador de Gonadotropina/metabolismo , Hipotálamo/metabolismo , Kisspeptinas/genética , Kisspeptinas/metabolismo , Masculino , Ocitocina/genética , Ocitocina/metabolismo , Plastificantes/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Ratos Sprague-Dawley , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Transcriptoma , Vasopressinas/genética , Vasopressinas/metabolismo
9.
Biomolecules ; 11(2)2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33557377

RESUMO

The synthetic estrogen diethylstilbestrol (DES) is used to treat metastatic carcinomas and prostate cancer. We studied its interaction with membranes and its localization to understand its mechanism of action and side-effects. We used differential scanning calorimetry (DSC) showing that DES fluidized the membrane and has poor solubility in DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) in the fluid state. Using small-angle X-ray diffraction (SAXD), it was observed that DES increased the thickness of the water layer between phospholipid membranes, indicating effects on the membrane surface. DSC, X-ray diffraction, and 31P-NMR spectroscopy were used to study the effect of DES on the Lα-to-HII phase transition, and it was observed that negative curvature of the membrane is promoted by DES, and this effect may be significant to understand its action on membrane enzymes. Using the 1H-NOESY-NMR-MAS technique, cross-relaxation rates for different protons of DES with POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) protons were calculated, suggesting that the most likely location of DES in the membrane is with the main axis parallel to the surface and close to the first carbons of the fatty acyl chains of POPC. Molecular dynamics simulations were in close agreements with the experimental results regarding the location of DES in phospholipids bilayers.


Assuntos
Varredura Diferencial de Calorimetria/métodos , Carbono/química , Dietilestilbestrol/química , Ácidos Graxos/química , Membranas Artificiais , Difração de Raios X/métodos , Dietilestilbestrol/análise , Bicamadas Lipídicas/química , Espectroscopia de Ressonância Magnética , Simulação de Dinâmica Molecular , Transição de Fase , Fosfatidilcolinas/química , Fosfolipídeos/química , Radioisótopos de Fósforo/química , Prótons , Solubilidade , Temperatura , Termodinâmica
11.
Hum Reprod ; 36(1): 82-86, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33147330

RESUMO

To date, vaginal/cervical clear cell adenocarcinoma (CCAC) has not been reported in the granddaughters of women treated with diethylstilbestrol (DES) during pregnancy. We present an 8-year-old girl with a history of severe vaginal bleeding who was diagnosed with cervical CCAC. She underwent fertility-sparing surgery and radiotherapy. No sign of recurrence was detected throughout a 10-year follow-up. Her grandmother had received DES therapy during pregnancy with the patient's mother. Although no direct causal link is demonstrated, this case raises for the first time, the hypothesis of multigenerational effects of DES in girls and strongly suggests the need to follow the granddaughters of DES-treated women.


Assuntos
Adenocarcinoma de Células Claras , Disruptores Endócrinos , Efeitos Tardios da Exposição Pré-Natal , Adenocarcinoma de Células Claras/induzido quimicamente , Colo do Útero , Criança , Dietilestilbestrol/efeitos adversos , Feminino , Humanos , Recidiva Local de Neoplasia , Gravidez
12.
Artigo em Inglês | MEDLINE | ID: mdl-32710933

RESUMO

Hormonal sex reversal can produce monosex fish stocks and provide insights into their gamity and reproductive physiology. However, paradoxical effects have been reported in several fish species that remain largely ignored as anomalies, particularly those of masculinisation. As a first step, this study examined reproductive viability of paradoxically masculinised Gambusia holbrooki produced following oral administration (20-100 mg/kg feed) of a feminizing hormone diethylstilbestrol (DES). Contrary to expectation, all treatment groups produced 100% male populations. Survival, mating behaviour, gamete production, breeding output as well as expression of anti-Mullerian hormone (amh), ovarian (cyp19a1a) and brain (cyp19a1b) aromatase of masculinised fish were also examined. Survival (≤ 54.1 ± 7.3%) at termination of DES treatment was significantly lower compared with controls (88.6 ± 4.3%) but remained unaffected post treatment. Gonopodium thrusting frequency (33 ± 9.8 per 10 min) was not significantly different to untreated males just as sperm abundance (3.9 ± 1.5 × 108/male) and their motility (88.6 ± 29.1%). Importantly, paradoxically masculinised fish mated with virgin females and produced clutch sizes (22 ± 4) and progeny survival (87.0 ± %) that were comparable to that of untreated males. Masculinised testes showed high amh and low cyp19a1a expression, a pattern resembling those of untreated males. Production of paradoxically sex-reversed males with a capability to produce viable offspring has not been reported previously in this or other fish species. The outcomes support a feed-back regulation of oestrogenic pathways in this viviparous fish and could be useful for ecological applications such as controlling invasive fish populations.


Assuntos
Ciprinodontiformes/fisiologia , Dietilestilbestrol/farmacologia , Ovário/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Hormônio Antimülleriano/metabolismo , Aromatase/genética , Aromatase/metabolismo , Transtornos do Desenvolvimento Sexual/induzido quimicamente , Estrogênios não Esteroides/farmacologia , Feminino , Masculino , Ovário/fisiologia , Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologia , Testículo/fisiologia
13.
Stem Cell Rev Rep ; 16(5): 893-908, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32592162

RESUMO

Reproductive health of men has declined in recent past with reduced sperm count and increased incidence of infertility and testicular cancers mainly attributed to endocrine disruption in early life. Present study aims to evaluate whether testicular stem cells including very small embryonic-like stem cells (VSELs) and spermatogonial stem cells (SSCs) get affected by endocrine disruption and result in pathologies in adult life. Effect of treatment on mice pups with estradiol (20 µg on days 5-7) and diethylstilbestrol (DES, 2 µg on days 1-5) was studied on VSELs, SSCs and spermatogonial cells in adult life. Treatment affected spermatogenesis, tubules in Stage VIII & sperm count were reduced along with reduction of meiotic (4n) cells and markers (Prohibitin, Scp3, Protamine). Enumeration of VSELs by flow cytometry (2-6 µm, 7AAD-, LIN-CD45-SCA-1+) and qRT-PCR using specific transcripts for VSELs (Oct-4a, Sox-2, Nanog, Stella, Fragilis), SSCs (tOct-4, Gfra-1, Gpr-125) and early germ cells (Mvh, Dazl) showed several-fold increase but transition from c-Kit negative to c-Kit positive spermatogonial cells was blocked on D100 after treatment. Transcripts specific for apoptosis (Bcl2, Bax) remained unaffected but tumor suppressor (p53) and epigenetic regulator (NP95) transcripts showed marked disruption. 9 of 10 mice exposed to DES showed tumor-like changes. To conclude, endocrine disruption resulted in a tilt towards excessive self-renewal of VSELs (leading to testicular cancer after DES treatment) and blocked differentiation (reduced numbers of c-Kit positive cells, meiosis, sperm count and fertility). Understanding the underlying basis for infertility and cancer initiation from endogenous stem cells through murine modelling will hopefully improve human therapies in future.


Assuntos
Envelhecimento/patologia , Carcinogênese/patologia , Células-Tronco Embrionárias/patologia , Disruptores Endócrinos/toxicidade , Fertilidade/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/patologia , Espermatogênese/efeitos dos fármacos , Testículo/patologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Carcinogênese/genética , Dietilestilbestrol/toxicidade , Células-Tronco Embrionárias/efeitos dos fármacos , Células-Tronco Embrionárias/metabolismo , Feminino , Fertilidade/genética , Hormônio Foliculoestimulante/genética , Hormônio Foliculoestimulante/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônio Luteinizante/genética , Hormônio Luteinizante/metabolismo , Masculino , Camundongos , Modelos Biológicos , Tamanho do Órgão/efeitos dos fármacos , Ploidias , Gravidez , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Transcrição SOX9/metabolismo , Espermatogênese/genética
14.
Int J Mol Sci ; 21(11)2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32486162

RESUMO

Obstructive voiding disorder (OVD) occurs during aging in men and is often, but not always, associated with increased prostate size, due to benign prostatic hyperplasia (BPH), prostatitis, or prostate cancer. Estrogens are known to impact the development of both OVD and prostate diseases, either during early urogenital tract development in fetal-neonatal life or later in adulthood. To examine the potential interaction between developmental and adult estrogen exposure on the adult urogenital tract, male CD-1 mice were perinatally exposed to bisphenol A (BPA), diethylstilbestrol (DES) as a positive control, or vehicle negative control, and in adulthood were treated for 4 months with Silastic capsules containing testosterone and estradiol (T+E2) or empty capsules. Animals exposed to BPA or DES during perinatal development were more likely than negative controls to have urine flow/kidney problems and enlarged bladders, as well as enlarged prostates. OVD in adult T+E2-treated perinatal BPA and DES animals was associated with dorsal prostate hyperplasia and prostatitis. The results demonstrate a relationship between elevated exogenous estrogen levels during urogenital system development and elevated estradiol in adulthood and OVD in male mice. These findings support the two-hit hypothesis for the development of OVD and prostate diseases.


Assuntos
Compostos Benzidrílicos/toxicidade , Dietilestilbestrol/toxicidade , Estradiol/farmacologia , Fenóis/toxicidade , Testosterona/farmacologia , Obstrução Uretral/fisiopatologia , Animais , Bioensaio , Feminino , Hidronefrose , Rim/patologia , Masculino , Camundongos , Tamanho do Órgão , Gravidez , Prenhez , Efeitos Tardios da Exposição Pré-Natal , Próstata/patologia , Hiperplasia Prostática/patologia , Prostatite/patologia , Bexiga Urinária/patologia
15.
Zygote ; 28(4): 322-332, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32340635

RESUMO

Transparent Casper zebrafish allow studies of vertebrate sexual maturation and gonad development in vivo. Casper gonad dynamics can be observed longitudinally over time and non-invasively. Gonad maturation and reproduction are complex processes subject to disruption by endocrine-disrupting chemicals (EDCs), such as diethylstilbestrol (DES). DES was used as a 'proof of principle' to ascertain the usefulness of the Casper model to determine EDC effects on gonad maturation. Puberty onset in control juvenile Casper zebrafish (N = 43) averaged 13.2 weeks post fertilization (WPF) for females and included increased vent size, while in males puberty occurred at 11.7 WPF along with maintenance of small vents. DES treatment for 6 days in early juveniles (N = 20) induced an average delay in puberty of 5 weeks in females and 10 weeks in males. DES induced loss of breeding tubercles and vent enlargement in post-pubescent males. Puberty in control fish was correlated with an average body length of 1.7 cm for males and 1.8 cm for females. Increased testes opacity, small vent and breeding tubercles denoted male puberty. Puberty in females was defined as ovarian follicle diameters reaching 400 µm with increasingly opaque follicles and by an increased vent size. These results are like those for wild-type zebrafish and indicate that the Casper model is a useful system for studying gonad dynamics in vivo. Future use of transgenic reporter lines in Casper will allow new avenues of investigation into the reproductive biology of this vertebrate model.


Assuntos
Folículo Ovariano/crescimento & desenvolvimento , Maturidade Sexual/fisiologia , Testículo/crescimento & desenvolvimento , Peixe-Zebra/crescimento & desenvolvimento , Animais , Animais Geneticamente Modificados , Dietilestilbestrol/farmacologia , Disruptores Endócrinos/farmacologia , Feminino , Masculino , Folículo Ovariano/citologia , Folículo Ovariano/efeitos dos fármacos , Ovário/efeitos dos fármacos , Ovário/crescimento & desenvolvimento , Maturidade Sexual/efeitos dos fármacos , Testículo/efeitos dos fármacos , Peixe-Zebra/genética
16.
Cochrane Database Syst Rev ; 4: CD004198, 2020 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-32251534

RESUMO

BACKGROUND: Sickle cell disease comprises a group of genetic haemoglobin disorders. The predominant symptom associated with sickle cell disease is pain resulting from the occlusion of small blood vessels by abnormally 'sickle-shaped' red blood cells. There are other complications, including chronic organ damage and prolonged painful erection of the penis, known as priapism. Severity of sickle cell disease is variable, and treatment is usually symptomatic. Priapism affects up to half of all men with sickle cell disease, however, there is no consistency in treatment. We therefore need to know the best way of treating this complication in order to offer an effective interventional approach to all affected individuals. This is an update of a previously published review. OBJECTIVES: To assess the benefits and risks of different treatments for stuttering (repeated short episodes) and fulminant (lasting for six hours or more) priapism in sickle cell disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched trial registries. Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 09 September 2019. Date of most recent search of trial registries and of Embase: 01 October 2019. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing non-surgical or surgical treatment with placebo or no treatment, or with another intervention for stuttering or fulminant priapism. DATA COLLECTION AND ANALYSIS: The authors independently extracted data and assessed the risk of bias of the trials. MAIN RESULTS: Three trials with 102 participants were identified and met the criteria for inclusion in this review. These trials compared stilboestrol to placebo, sildenafil to placebo and a four-arm trial which compared ephedrine or etilefrine to placebo and ranged in duration from two weeks to six months. All of the trials were conducted in an outpatient setting in Jamaica, Nigeria and the UK. None of the trials measured our first primary outcome, detumescence. However, all three trials reported on the reduction in frequency of stuttering priapism, our second primary outcome; and from the evidence included in this review, we are uncertain whether stilboestrol, etilefrine or ephedrine reduce the frequency of stuttering priapism as the certainty of the evidence has been assessed as very low. Additionally, we conclude that sildenafil may make little or no difference (low-certainty evidence). Two trials reported on immediate side effects and we are uncertain whether etilefrine or ephedrine reduce the occurrence of these (very low-certainty of evidence) and also conclude that sildenafil may make little or no difference in side effects (low-quality evidence). Given that all of the trials were at risk of bias and all had low participant numbers, we considered the certainty of the evidence to be low to very low. AUTHORS' CONCLUSIONS: There is a lack of evidence for the benefits or risks of the different treatments for both stuttering and fulminant priapism in sickle cell disease. This systematic review has clearly identified the need for well-designed, adequately-powered, multicentre randomised controlled trials assessing the effectiveness of specific interventions for priapism in sickle cell disease.


Assuntos
Anemia Falciforme/complicações , Dietilestilbestrol/uso terapêutico , Estrogênios não Esteroides/uso terapêutico , Priapismo/tratamento farmacológico , Vasoconstritores/uso terapêutico , Adrenérgicos/efeitos adversos , Adrenérgicos/uso terapêutico , Efedrina/efeitos adversos , Efedrina/uso terapêutico , Etilefrina/efeitos adversos , Etilefrina/uso terapêutico , Humanos , Masculino , Priapismo/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Citrato de Sildenafila/uso terapêutico , Taquicardia/induzido quimicamente , Vasoconstritores/efeitos adversos , Adulto Jovem
17.
J Toxicol Sci ; 45(3): 131-136, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32147636

RESUMO

Reproductive disorders in birds are the most characteristic effects of DDT contamination of wildlife. Experimental exposure of avian eggs to the estrogenic substance o,p'-DDT causes abnormal development of the reproductive tract (shortening of the left oviduct and aberrant development of the right oviduct) and eggshell thinning in mature birds, but it is still not known how eggshell thinning occurs in the abnormal oviduct. To fill this information gap, we examined the histology of the uterine part of the oviduct in Japanese quail treated in ovo with o,p'-DDT or a synthetic estrogen, diethylstilbestrol (DES), and we performed immunohistochemical staining for the calcium-binding proteins CALB1, SPP1, and TRPV6. Both o,p'-DDT-treated and DES-treated quail had few, and scattered, gland cells in the left uterus, unlike vehicle controls, in which gland cells tightly occupied the lamina propria. The aberrantly developed right uterus retained all the components of the normal left uterus, but in immature form. Immunostaining for CALB1, SPP1, and TRPV6 was greatly reduced by both o,p'-DDT and DES; SPP1 and TRPV6 immunostaining patterns, in particular, differed distinctly from those in the controls. These findings suggest that CALB1, SPP1, and TRPV6 are molecular factors, decreased production of which is responsible for eggshell thinning. Our findings also could contribute to understanding of the eggshell formation mechanism in birds.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , DDT/toxicidade , Casca de Ovo/efeitos dos fármacos , Oviductos/efeitos dos fármacos , Oviductos/metabolismo , Animais , Coturnix , Dietilestilbestrol/toxicidade , Casca de Ovo/patologia , Feminino , Oviductos/patologia
18.
Hum Reprod Update ; 26(3): 412-422, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32141508

RESUMO

BACKGROUND: Despite its high prevalence and health burden, many aspects of endometriosis remain unclear, including risk factors and the underlying biological mechanisms. Exposures during early life, including in utero, are thought to play an important role in the subsequent onset of the condition. To date, however, much of the evidence from studies on early life exposures and diagnosed endometriosis appears mixed and difficult to assess. OBJECTIVE AND RATIONALE: This study aims to provide a systematic review of the epidemiologic evidence on early life factors associated with the subsequent diagnosis of endometriosis. In utero and early life exposures have previously been linked to a range of adult health outcomes, including infertility. SEARCH METHODS: A systematic review of case-control, cross-sectional and cohort studies was conducted using the search terms 'endometriosis'[MeSH] AND ('risk factors'[MeSH] OR 'protective factors'[MeSH]) AND ('in utero', 'fetal', 'neonatal, 'perinatal', 'developmental origins', 'early life', 'childhood' OR 'life course') in Embase, PubMed and Scopus databases. The review included articles published in English until 10 June 2018 with original data from studies with diagnosed endometriosis. The quality of primary studies was evaluated using the Newcastle-Ottawa Scale by both authors independently. Due to the degree of inconsistency in the measurements and study methods, a qualitative assessment of findings was undertaken rather than meta-analysis. OUTCOMES: The search retrieved 70 records without duplicates that contained 20 records on human case-control, cross-sectional or cohort studies, from which 11 papers/studies were selected based on their assessment score. The majority of studies found that women born with low birthweight (<2.5 kg or <5.5 lb) were more likely to be diagnosed with endometriosis. For other early life factors, the evidence is mixed or limited, with further research needed on the association of endometriosis with preterm birth, in utero exposure to diethylstilbestrol and to maternal smoking, passive smoking in early life, and infant formula feeding (compared with breastfeeding). WIDER IMPLICATIONS: While the weight of evidence points to low birthweight as a risk factor for diagnosis of endometriosis, future research is warranted on this and other key early life exposures where the findings are mixed to provide more robust evidence and for insights on potential causal pathways. Such research, however, needs to address current methodological issues, such as the use of prospective data from large population-based studies, better diagnostic methods to confirm disease free status, more consistent definitions of variables and consideration of potential biological mechanisms to guide the analyses. The improvements will advance the future synthesis of evidence to support clinically relevant risk assessment for a more timely diagnosis and treatment of endometriosis.


Assuntos
Endometriose/epidemiologia , Endometriose/patologia , Recém-Nascido de Baixo Peso/fisiologia , Nascimento Prematuro/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Estudos de Casos e Controles , Criança , Estudos de Coortes , Estudos Transversais , Dietilestilbestrol/efeitos adversos , Feminino , Humanos , Fórmulas Infantis/efeitos adversos , Recém-Nascido , Gravidez , Cuidado Pré-Natal , Estudos Prospectivos , Fatores de Risco , Poluição por Fumaça de Tabaco/efeitos adversos
19.
Analyst ; 145(9): 3306-3312, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32195485

RESUMO

In this work, a sensitive and selective electrochemiluminescent aptasensor was proposed based on the enhancing mechanism of the metal-organic framework NH2-MIL-125(Ti) in a 3,4,9,10-perylenetetracarboxylic acid/K2S2O8 system for a diethylstilbestrol assay. Herein, 3,4,9,10-perylenetetracarboxylic acid was selected as the major luminophore, and the metal-organic framework NH2-MIL-125(Ti) displayed a large specific surface area to immobilize abundant PTCA molecules to facilitate electrochemiluminescence efficiency. Besides, the metal-organic framework NH2-MIL-125(Ti) was used as a novel catalyst in the 3,4,9,10-perylenetetracarboxylic acid/K2S2O8 system, which could react with the co-reactant K2S2O8 to produce more SO4˙-. In addition, we introduced the amino-aptamer of diethylstilbestrol; due to the specific binding affinity between the aptamer and diethylstilbestrol, a selective electrochemiluminescent aptasensor for diethylstilbestrol was thus developed here. Under the optimal conditions, a wide detection range from 1.0 fM to 1.0 µM with a low detection limit of 0.28 fM (S/N = 3) was obtained. More importantly, the residual diethylstilbestrol in water was detected by the developed aptasensor; this confirmed that this method has good performance and potential applications in real samples.


Assuntos
Aptâmeros de Nucleotídeos/química , Dietilestilbestrol/análise , Medições Luminescentes/métodos , Estruturas Metalorgânicas/química , Perileno/análogos & derivados , Compostos de Potássio/química , Sulfatos/química , Catálise , Dietilestilbestrol/química , Técnicas Eletroquímicas , Eletrodos , Água Doce/análise , Limite de Detecção , Perileno/química , Reprodutibilidade dos Testes , Titânio/química
20.
Int J Mol Sci ; 21(4)2020 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-32102189

RESUMO

Endocrine disrupting chemicals (EDCs) are exogenous substances that interfere with the stability and regulation of the endocrine system of the body or its offspring. These substances are generally stable in chemical properties, not easy to be biodegraded, and can be enriched in organisms. In the past half century, EDCs have gradually entered the food chain, and these substances have been frequently found in maternal blood. Perinatal maternal hormone levels are unstable and vulnerable to EDCs. Some EDCs can affect embryonic development through the blood-fetal barrier and cause damage to the neuroendocrine system, liver function, and genital development. Some also effect cross-generational inheritance through epigenetic mechanisms. This article mainly elaborates the mechanism and detection methods of estrogenic endocrine disruptors, such as bisphenol A (BPA), organochlorine pesticides (OCPs), diethylstilbestrol (DES) and phthalates (PAEs), and their effects on placenta and fetal health in order to raise concerns about the proper use of products containing EDCs during pregnancy and provide a reference for human health.


Assuntos
Disruptores Endócrinos/efeitos adversos , Feto/efeitos dos fármacos , Praguicidas/efeitos adversos , Placenta/efeitos dos fármacos , Animais , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/sangue , Líquidos Corporais/química , Dietilestilbestrol/efeitos adversos , Dietilestilbestrol/sangue , Disruptores Endócrinos/administração & dosagem , Disruptores Endócrinos/sangue , Disruptores Endócrinos/metabolismo , Feminino , Humanos , Hidrocarbonetos Clorados/efeitos adversos , Hidrocarbonetos Clorados/sangue , Sistemas Neurossecretores/efeitos dos fármacos , Praguicidas/sangue , Praguicidas/metabolismo , Fenóis/efeitos adversos , Fenóis/sangue , Ácidos Ftálicos/efeitos adversos , Ácidos Ftálicos/sangue , Gravidez
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...