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1.
Chem Biol Interact ; 338: 109402, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33587916

RESUMO

Cisplatin is an important antineoplastic drug used in multiple chemotherapeutic regimens but unfortunately causes serious toxic effects as ovarian and uterine toxicity. This study aimed to investigate the potential protective effect of resveratrol (RSV) against cisplatin-induced ovarian and uterine toxicity in female rats. Thirty-two female Wistar rats were divided randomly into four groups (n = 8 in each). Control group received oral normal saline for 28 days; RSV group received RSV (10 mg/kg; daily) via oral gavage; CIS group received a single dose of CIS (7 mg/kg; i.p.) on the 21st day; (CIS + RSV) group received both RSV and CIS by the same schedules and doses of RSV and CIS groups, respectively. Results demonstrated a significant decrease in MDA level and a significant increase in both glutathione content and activity of the antioxidant enzymes GPx, SOD, and CAT in the tissues of the ovary and uterus of CIS + RSV group in comparison to that of CIS group (P<0.05), also there are significantly decreased tissue levels of the proinflammatory cytokines and enzymes (NF-κB, IL-1ß, IL-6, TNF-α, COX-2, and iNOS), increased estradiol, progesterone, prolactin and decreased FSH serum levels in CIS + RSV group compared to CIS group (P < 0.05). Moreover, there is downregulation of tissues Cleaved Caspase-3, NF-κB and Cox-2 proteins as shown in Western blot analysis, also apoptosis was significantly inhibited, evidenced by downregulation of Bax and upregulation of Bcl-2 proteins, and the ovarian and uterine histological architecture and integrity were maintained in CIS + RSV group compared to CIS group. In conclusion, these findings indicate that RSV has beneficial effects in ameliorating cisplatin-induced oxidative stress, inflammation, and apoptosis in the ovarian and uterine tissues of female rats.


Assuntos
Apoptose/efeitos dos fármacos , Cisplatino/efeitos adversos , Inflamação/patologia , Ovário/patologia , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Resveratrol/farmacologia , Útero/patologia , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Catalase/metabolismo , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Malondialdeído/metabolismo , Modelos Biológicos , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Ovário/efeitos dos fármacos , Progesterona/sangue , Prolactina/sangue , Carbonilação Proteica/efeitos dos fármacos , Ratos Wistar , Superóxido Dismutase/metabolismo , Proteína X Associada a bcl-2/metabolismo
2.
Nat Commun ; 12(1): 1064, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33594056

RESUMO

Polycystic ovary syndrome (PCOS) is characterized by an oligo-anovulation, hyperandrogenism and polycystic ovarian morphology combined with major metabolic disturbances. However, despite the high prevalence and the human and economic consequences of this syndrome, its etiology remains unknown. In this study, we show that female Goto-Kakizaki (GK) rats, a type 2 diabetes mellitus model, encapsulate naturally all the reproductive and metabolic hallmarks of lean women with PCOS at puberty and in adulthood. The analysis of their gestation and of their fetuses demonstrates that this PCOS-like phenotype is developmentally programmed. GK rats also develop features of ovarian hyperstimulation syndrome. Lastly, a comparison between GK rats and a cohort of women with PCOS reveals a similar reproductive signature. Thus, this spontaneous rodent model of PCOS represents an original tool for the identification of the mechanisms involved in its pathogenesis and for the development of novel strategies for its treatment.


Assuntos
Síndrome do Ovário Policístico/patologia , Adiposidade , Animais , Animais Recém-Nascidos , Peso Corporal , Análise Discriminante , Modelos Animais de Doenças , Dislipidemias/patologia , Sistema Endócrino/patologia , Ciclo Estral , Feminino , Teste de Tolerância a Glucose , Gonadotropinas/farmacologia , Hormônios/sangue , Humanos , Secreção de Insulina , Análise dos Mínimos Quadrados , Lipídeos/química , Masculino , Troca Materno-Fetal , Análise Multivariada , Ovário/patologia , Ovário/fisiopatologia , Fenótipo , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/fisiopatologia , Gravidez , Ratos Wistar , Reprodução , Maturidade Sexual
3.
Ecotoxicol Environ Saf ; 212: 112012, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33550074

RESUMO

Microplastics (MPs) considered as a new persistent environmental pollutant could enter into the circulatory system and result in decrease of sperm quantity and quality in mice. However, the effects of Polystyrene MPs (PS MPs) on the ovary and its mechanism in rats remained unclear. In this present study, thirty-two healthy female Wistar rats were exposed to different concentrations of 0.5 µm PS MPs dispersed in deionized water for 90 days. Using hematoxylin-eosin (HE) staining, the number of growing follicles was decreased compared to the control group. In addition, the activity of glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD) were decreased while the expression level of malondialdehyde (MDA) was increased in ovary tissue. Confirmed by immunohistochemistry, the integrated optical density of NLRP3 and Cleaved-Caspase-1 had been elevated by 13.9 and 14 in granulosa cells in the 1.5 mg/kg/d group. Furthermore, compared to the control group, the level of AMH had been decreased by 23.3 pg/ml while IL-1ß and IL-18 had been increased by 32 and 18.5 pg/ml in the 1.5 mg/kg/d group using the enzyme-linked immune sorbent assay (ELISA). Besides, the apoptosis of granulosa cells was elevated measured by terminal deoxyribonucleotide transferase-mediated nick end labeling (TUNEL) staining and flow cytometry. Moreover, western blot assays showed that the expressions of NLRP3/Caspase-1 signaling pathway related factors and Cleaved-Caspase-3 were increased. These results demonstrated that PS MPs could induce pyroptosis and apoptosis of ovarian granulosa cells via the NLRP3/Caspase-1 signaling pathway maybe triggered by oxidative stress. The present study suggested that exposure to microplastics had adverse effects on ovary and could be a potential risk factor for female infertility, which provided new insights into the toxicity of MPs on female reproduction.


Assuntos
Apoptose/efeitos dos fármacos , Caspase 1/metabolismo , Microplásticos/toxicidade , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ovário/efeitos dos fármacos , Poliestirenos/toxicidade , Piroptose/efeitos dos fármacos , Animais , Feminino , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Células da Granulosa/patologia , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Malondialdeído/metabolismo , Ovário/metabolismo , Ovário/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Transdução de Sinais
4.
J Steroid Biochem Mol Biol ; 205: 105770, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33065278

RESUMO

The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with acute respiratory distress syndrome and infected patients have a relatively high risk of death. Emerging risk factors for poor outcome in this disease include age, male gender, cardiovascular co-morbidities including hypertension, prior cardiovascular disease, diabetes and more recently obesity. To date there are no data relating to SARS-CoV-2 in PCOS women. The present Clinical Opinion represents a summary of the epidemiological evidence and possible pathophysiological mechanisms regarding PCOS and COVID-19. PCOS women could be more susceptible to infections compared to non-PCOS women. Insulin resistance and the associated hyperinsulinaemia are drivers for enhanced steroidogenesis in women with PCOS. Weight-gain and obesity, through their worsening effects on insulin resistance, thereby drive enhanced steroidogenesis and hyperandrogenism. All these features represent key points to provide an explanation for the possible association between PCOS and SARS-CoV-2. Indeed, androgens may drive clinical results in COVID-19, through the expression of TMPRSS2, a cellular co-receptor necessary for SARS-CoV-2 infection and through androgen-mediated immune modulation. In women with PCOS the endocrine-immune axis leads to immune dysfunction with a state of chronic inflammation, and hyperandrogenism and IR with compensatory hyperglycaemia could play a determining role in the pathophysiogenesis of the infection. However, it is possible that only specific PCOS phenotypes may be more susceptible. In addition, vitamin D deficiency and gut dysbiosis are another important factor potentially involved in the increased risk of developing severe forms of COVID-19 in PCOS women. Further scientific investigations are needed with the aim of understanding which women are most at risk of becoming infected or developing complications, what are the causal mechanisms on which it is possible to intervene with prophylactic and therapeutic measures and what the long-term consequences will be on the health of these patients.


Assuntos
/epidemiologia , Inflamação/epidemiologia , Síndrome do Ovário Policístico/epidemiologia , Adulto , /genética , Feminino , Humanos , Hiperandrogenismo/complicações , Hiperandrogenismo/epidemiologia , Hiperandrogenismo/genética , Hiperandrogenismo/virologia , Inflamação/complicações , Inflamação/genética , Inflamação/virologia , Resistência à Insulina/genética , Ovário/metabolismo , Ovário/patologia , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/virologia , Fatores de Risco , /patogenicidade
5.
BMJ Case Rep ; 13(12)2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33370966

RESUMO

A 64-year-old postmenopausal female patient presented with approximately 5 years of intermittent spotting, progressive hirsutism and significantly increased libido and clitoral hypersensitivity with spontaneous orgasms multiple times a day beginning a few months prior. Initial hormone work-up revealed elevated total serum testosterone, androstenedione and 17-hydroxyprogesterone. Luteinising hormone, follicle stimulating hormone, estradiol, dehydroepiandrosterone-sulfate, thyroid stimulating hormone and prolactin were all within normal limits. Initial suspicions suggested an androgen-secreting tumour, likely in the ovary. The lesion was undetectable on transvaginal ultrasound and abdominal-pelvic CT scan. Laparoscopic bilateral salpingo-oophorectomy was performed to remove the likely source of excess androgens. Visible gross lesions were not observed intraoperatively; however, bilateral Leydig (hilus cell) tumours were confirmed by histopathology. Serum testosterone, androstenedione and 17-hydroxyprogesterone levels were normalised postoperatively within 2 weeks and 1 month, respectively.


Assuntos
Hirsutismo/etiologia , Tumor de Células de Leydig/diagnóstico , Neoplasias Ovarianas/diagnóstico , Ovário/patologia , 17-alfa-Hidroxiprogesterona/sangue , Androstenodiona/sangue , Feminino , Humanos , Tumor de Células de Leydig/sangue , Tumor de Células de Leydig/complicações , Tumor de Células de Leydig/cirurgia , Pessoa de Meia-Idade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/cirurgia , Ovário/cirurgia , Pós-Menopausa , Salpingo-Ooforectomia , Testosterona/sangue , Resultado do Tratamento
6.
Medicine (Baltimore) ; 99(41): e22625, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031322

RESUMO

RATIONALE: Giant ovarian tumors are very rare. Patients with large ovarian tumors appear similar to pregnant women and morbidly obese patients. The management of such patients is associated with significant mortality. Therefore, additional clinical research is essential to understanding the perioperative complications of this disease. PATIENT CONCERNS: We report the perioperative management of a patient with a giant ovarian tumor that contained 23 L of fluid who underwent tumor resection. Given the infrequency of these giant ovarian tumors, a detailed anesthetic plan and postoperative respiratory support strategy were tailored to address the patient's hemodynamic and respiratory risks, as well as to minimize potential complications, including supine hypotensive syndrome, re-expansion pulmonary edema, and postoperative intestinal ileus. To prevent supine hypotensive syndrome, the patient used a mild left-sided position (10∼20°) after admission until the tumor was removed. In order to prevent re-expansion pulmonary edema (RPE), the intraoperative ventilator mode was set to pressure-controlled ventilation (PCV), with the addition of 8 cmH2O positive end-expiratory pressure (PEEP). The airway pressure was lower while maintaining a certain tidal volume. In the ICU, in the ventilator mode, we use pressure support ventilation as well as PEEP and adjust it according to the patient's spontaneous breathing situation and blood gas analysis to prepare for further detach from the respirator and extubation. And we prevent the occurrence of postoperative intestinal ileus by placing the abdominal binder after the operation. DIAGNOSIS: Mucinous cystadenoma of the left ovary. INTERVENTIONS: The patient underwent exploratory laparotomy with debulking of the left ovarian mass, transabdominal hysterectomy with bilateral salpingo-oophorectomy, complete omentectomy with appendectomy, and pelvic lymphadenectomy. OUTCOMES: After surgery, the patient experienced intestinal distention. Up to now, the patient has recovered well. LESSONS: A multidisciplinary approach is essential. Knowing the possibility of complications and choices for management can lead to favorable outcomes in such rare cases. This case reminds us that postoperative complications such as postoperative intestinal ileus may be fatal.


Assuntos
Cistadenoma Mucinoso/cirurgia , Neoplasias Ovarianas/cirurgia , Assistência Perioperatória , Idoso , Anestesia , Cistadenoma Mucinoso/patologia , Feminino , Humanos , Neoplasias Ovarianas/patologia , Ovário/patologia
7.
Anticancer Res ; 40(11): 6017-6028, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33109540

RESUMO

BACKGROUND/AIM: R-spondins control WNT signaling and RSPO1 and LGR6, two of its receptors, are uniquely expressed at high levels in high-grade serous ovarian cancer (HGSOC). The aim of this study was to assess the interrelations between the expression of the RSPOs and LGRs in HGSOC and in the ovarian surface (OSE) and fallopian tube surface epithelium (FTSE) from which HGSOC arises. MATERIALS AND METHODS: Analysis of TCGA (HGSOC), CCLE (ovary), and other publicly accessed RNA-Seq data using UC San Diego Computational Cancer Analysis Library (CCAL) to perform differential expression analysis, association studies, and gene set inspection using the single-sample GSEA method. Additionally, we employed multiple publicly available databases including StringDB, Human Protein Atlas, and cBioPortal to aid the investigation. RESULTS: Among normal tissues, expression of RSPO1, LGR5 and LGR6 was highest in the fallopian tube. The relative levels of expression of the RSPOs and LGRs in the OSE and FTSE matched those in HGSOC. RSPO1 and LGR6 were highly co-expressed in all three tissues. Gene set enrichment analysis (GSEA) showed that expression of RSPO1 was strongly linked to the enrichment of three separate WNT-driven GO pathways. Analysis of genes that impacted overall survival identified two other immediately adjacent genes that control WNT signaling, KREMEN1 and ZNRF3 whose expression and copy number were coordinately linked. CONCLUSION: RSPO1 and LGR6 are coordinately expressed in HGSOC and the two normal tissues from which this tumor arises, and their expression is linked to WNT signaling pathways known the control cell fate and proliferation.


Assuntos
Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Receptores Acoplados a Proteínas-G/metabolismo , Trombospondinas/metabolismo , Via de Sinalização Wnt , Cistadenocarcinoma Seroso/genética , Tubas Uterinas/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Gradação de Tumores , Neoplasias Ovarianas/genética , Ovário/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Acoplados a Proteínas-G/genética , Trombospondinas/genética , Via de Sinalização Wnt/genética
8.
Ecotoxicol Environ Saf ; 205: 111338, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32956867

RESUMO

Lead (Pb) is well-recognized for its great hazards to human and wildlife health. It has negative influences on multiple organs and systems of birds. Especially, lead exposure caused adverse impacts on bird reproduction. In this study, one week old female Japanese quails were randomly allocated into four groups and each group was respectively fed with 0, 50 ppm, 500 ppm and 1000 ppm Pb in drinking water for 36 days to determine the effects of chronic lead exposure on ovarian development and function. The results showed that Pb did accumulate in the ovary and ovarian development was delayed by high dose lead exposure (500 ppm and 1000 ppm). Moreover, high Pb dosage induced ovarian histopathological damages characterized by granulosa cells disorganization, follicle atresia and interstitial cell degeneration. Meanwhile, the concentration of estradiol (E2) was significantly decreased and mRNA levels of genes involved with ovarian steroidogenesis were significantly down-regulated by high concentration Pb. In addition, Pb exposure caused increasing cell apoptosis and significant changes of the expression of genes involved with cell death in the ovary. High dose Pb exposure also inhibited thyroid hormone release and disrupted ovarian thyroid deiodination apart from causing thyroid histopathological injury such as follicular deformation and atrophy. The study indicated that Pb might cause ovarian malfunction by inducing ovary and thyroid microstructural damages, thyroid hormone and estrogen release inhibition and ovarian steroidogenesis disruption.


Assuntos
Coturnix/metabolismo , Poluentes Ambientais/toxicidade , Estradiol/metabolismo , Expressão Gênica/efeitos dos fármacos , Chumbo/toxicidade , Ovário/efeitos dos fármacos , Hormônios Tireóideos/metabolismo , Adolescente , Animais , Apoptose/efeitos dos fármacos , Coturnix/genética , Coturnix/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Poluentes Ambientais/metabolismo , Estradiol/genética , Feminino , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/patologia , Humanos , Chumbo/metabolismo , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/patologia , Ovário/crescimento & desenvolvimento , Ovário/metabolismo , Ovário/patologia , Distribuição Aleatória , Reprodução/efeitos dos fármacos , Reprodução/genética , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Hormônios Tireóideos/genética
9.
Anticancer Res ; 40(10): 5869-5875, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988917

RESUMO

BACKGROUND/AIM: We aimed to identify differences in cytoreduction rates and procedures performed in patients with advanced ovarian cancer undergoing primary (PDS) or interval debulking surgery (IDS). PATIENTS AND METHODS: Data were collected prospectively on 110 consecutive patients from June 2016 to Mar 2020. RESULTS: Forty-nine patients (44.5%) underwent diaphragmatic peritonectomy (34 in PDS and 15 in IDS, p=0.005), while 38 (34.5%) underwent large bowel resection (29 in PDS and 9 in IDS, p<0.001). Complete cytoreduction was achieved in 39 patients in PDS and 29 in IDS (65% vs. 58%, p=0.22). Longer operations with more blood loss and extended hospital stay were performed in the PDS group. Ten patients (9.1%) experienced severe complications and in eight patients (7.2%) chemotherapy was delayed. CONCLUSION: More bowel resections and diaphragmatic stripping were performed in the PDS group. End surgical results were similar between groups, with a trend for more complete cytoreduction in PDS.


Assuntos
Procedimentos Cirúrgicos de Citorredução , Neoplasias Ovarianas/cirurgia , Ovário/cirurgia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia Adjuvante , Feminino , Humanos , Tempo de Internação , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Ovário/patologia
10.
Life Sci ; 261: 118353, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32877649

RESUMO

AIMS: Polycystic ovary syndrome (PCOS) is a widespread chronic reproductive disorder that is associated with metabolic disturbances. Traditionally, the marjoram plant is well-known to restore hormonal balance and regulate the menstrual cycle. We aimed to investigate the ameliorative effects of marjoram extract on hormonal profiles, body and ovaries weight, insulin sensitivity, inflammation, and oxidative stress in a rat model of PCOS. MAIN METHODS: A 75 postpubertal (42 days old) female Wistar rats were randomly assigned into five groups (control, dehydroepiandrosterone (DHEA) induced-PCOS model, marjoram-treated PCOS rats, metformin-treated PCOS rats and the combination of marjoram+metfomin treated PCOS model). PCOS induction was performed by subcutaneous injection of DHEA 60 mg/kg daily for 24 days. Ovaries weight, adiponectin, hormonal levels, inflammatory, and oxidative stress biomarker levels were measured at the end of the treatment period using ELISA assay. KEY FINDINGS: The current study showed that marjoram significantly decreased ovaries' weight and the estradiol levels (P-value<0.05) compared to the DHEA group. Interestingly, marjoram improved insulin sensitivity as manifested by a significant increase in the adiponectin serum levels (P-value<0.05). Marjoram alone or in combination with metformin prominently decreased the IL-6 level and improved the levels of ovarian SOD and GPx enzymes (P-value<0.05). Additionally, the group treated with the combination of marjoram and metformin remarkably decreased the level of TBARS (P-value<0.05). SIGNIFICANCE: The present study established the beneficial effects of marjoram administration on DHEA-induced PCOS in female Wistar rats. The mechanistic effect includes improvement in the hormonal levels, ovaries weight, insulin sensitivity, antioxidants, and anti-inflammatory parameters.


Assuntos
Origanum/química , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/tratamento farmacológico , Adiponectina/sangue , Animais , Biomarcadores/sangue , Peso Corporal/efeitos dos fármacos , Desidroepiandrosterona , Feminino , Hormônios Esteroides Gonadais/sangue , Mediadores da Inflamação/sangue , Tamanho do Órgão/efeitos dos fármacos , Ovário/efeitos dos fármacos , Ovário/patologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Síndrome do Ovário Policístico/sangue , Ratos Wistar
11.
Medicine (Baltimore) ; 99(30): e20387, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791659

RESUMO

RATIONALE: Ovarian small cell carcinoma of hypercalcemic type (OSCCHT) is a relatively rare and highly fatal gynecological malignancy of unknown histogenesis, affecting mainly girls and young women. OSCCHT occurring during pregnancy is an uncommon event, and preoperative diagnosis of this malignancy is much more difficult in pregnant than non-pregnant women. The aim of this study was to describe a rare case of primary OSCCHT in a pregnant woman and to review the current literature. PATIENT CONCERNS: Here we present a case of OSCCHT in a 21-year-old patient in the 32nd week of gestation, who had abdominal pain and irregular vaginal bleeding for 5 hours. Because placental abruption, stillbirth, and hemorrhagic shock were suspected, she subsequently underwent diagnostic laparotomy. During the hysterotomy delivery and exploratory laparotomy, we found a dead fetus in the uterus and a large tumor mass arising from her left ovary. Plasma-based detection showed that the patient had a slightly elevated parathyroid hormone (PTH) level and normal serum calcium. After surgery, her serum PTH levels returned to normal. DIAGNOSIS AND INTERVENTIONS: The patient was initially treated with surgery. She underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, as well as the following additional procedures: appendectomy, sigmoidectomy, debulking of extra-ovarian tumor, lymph node dissection, and peritoneal biopsies. The patient, who was in the third trimester of pregnancy, was diagnosed with OSCCHT that was confirmed to be Stage III. She was recommended chemotherapy after surgery, but she declined chemotherapy. OUTCOMES: Unfortunately, the patient died 5 months after surgery. LESSONS: OSCCHT is a very rare and highly aggressive tumor type. The clinical symptoms of this tumor are nonspecific, and pathological examination remains the gold standard for diagnosis. Most patients are diagnosed with advanced stage disease and do not respond to chemotherapy. The prognosis of OSCCHT is generally poor, and no treatment guidelines are available as yet. For pregnant woman, OSCCHT is especially harmful to the mother and may indirectly lead to the death of the fetus.


Assuntos
Carcinoma de Células Pequenas/patologia , Neoplasias Ovarianas/patologia , Ovário/patologia , Complicações Neoplásicas na Gravidez/patologia , Feminino , Humanos , Gravidez , Adulto Jovem
12.
Ecotoxicol Environ Saf ; 205: 111176, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32846301

RESUMO

The effects of 17α-ethinylestradiol (EE2) on sex ratio, gonopodium morphology, and gonadal histology of C. decemmaculatus were assessed by a full-lifecycle exposure experiment. Newborn fish were waterborne exposed to 30, 100, and 300 ng EE2/L for 90 d, using 50 fish per treatment. Additionally, in December of 2016, a field survey was conducted on a C. decemmaculatus population inhabiting the Girado Creek downstream of the Chascomus city wastewater effluent discharge. After 90 d of exposure, EE2 was able to histologically skew the sex ratio toward females and inhibit the full gonopodium development since the lowest tested concentration (LOEC = 30 ng/L). At higher concentrations, EE2 was toxic, inducing mortality in a concentration-dependent fashion (90 d-LC50 = 109.9 ng/L) and altering the gonadal histoarchitecture, causing neither testes nor ovaries discernible histologically (LOEC = 100 ng/L). In addition, a novel response, perianal hyperpigmentation, was discovered been induced by the EE2 exposure in a concentration-dependent fashion (90 d-EC50 = 39.3 ng/L). A higher proportion of females and perianal hyperpigmentation were observed in wild fish collected from the Girado Creek. The major reached conclusions are: i) EE2 induce different effects on the sexual traits of C. decemmaculatus when exposed from early-life or adult stages. ii) The most sensitive effects observed in the laboratory occur in a creek receiving wastewater effluent. iii) The perianal hyperpigmentation comes-up as a promising biomarker of exposure to estrogenic compounds.


Assuntos
Ciprinodontiformes/crescimento & desenvolvimento , Disruptores Endócrinos/toxicidade , Etinilestradiol/toxicidade , Gônadas/efeitos dos fármacos , Hiperpigmentação/induzido quimicamente , Poluentes Químicos da Água/toxicidade , Animais , Relação Dose-Resposta a Droga , Feminino , Gônadas/crescimento & desenvolvimento , Gônadas/patologia , Humanos , Estágios do Ciclo de Vida/efeitos dos fármacos , Masculino , Ovário/efeitos dos fármacos , Ovário/crescimento & desenvolvimento , Ovário/patologia , Fenótipo , Razão de Masculinidade , Testículo/efeitos dos fármacos , Testículo/crescimento & desenvolvimento , Testículo/patologia
13.
Int J Nanomedicine ; 15: 4333-4350, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606681

RESUMO

Background: Different diseases affect both mechanical and chemical features of the involved tissue, enhancing the symptoms. Methods: In this study, using atomic force microscopy, we mechanically characterized human ovarian tissues with four distinct pathological conditions: mucinous, serous, and mature teratoma tumors, and non-tumorous endometriosis. Mechanical elasticity profiles were quantified and the resultant data were categorized using K-means clustering method, as well as fuzzy C-means, to evaluate elastic moduli of cellular and non-cellular parts of diseased tissues and compare them among four disease conditions. Samples were stained by hematoxylin-eosin staining to further study the content of different locations of tissues. Results: Pathological state vastly influenced the mechanical properties of the ovarian tissues. Significant alterations among elastic moduli of both cellular and non-cellular parts were observed. Mature teratoma tumors commonly composed of multiple cell types and heterogeneous ECM structure showed the widest range of elasticity profile and the stiffest average elastic modulus of 14 kPa. Samples of serous tumors were the softest tissues with elastic modulus of only 400 Pa for the cellular part and 5 kPa for the ECM. Tissues of other two diseases were closer in mechanical properties as mucinous tumors were insignificantly stiffer than endometriosis in cellular part, 1300 Pa compared to 1000 Pa, with the ECM average elastic modulus of 8 kPa for both. Conclusion: The higher incidence of carcinoma out of teratoma and serous tumors may be related to the intense alteration of mechanical features of the cellular and the ECM, serving as a potential risk factor which necessitates further investigation.


Assuntos
Microscopia de Força Atômica , Nanopartículas/química , Ovário/patologia , Ovário/ultraestrutura , Adulto , Fenômenos Biomecânicos , Módulo de Elasticidade , Matriz Extracelular/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade
14.
Anticancer Res ; 40(8): 4795-4800, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727807

RESUMO

BACKGROUND/AIM: This study aimed to use artificial intelligence (AI) to predict the pathological diagnosis of ovarian tumors using patient information and data from preoperative examinations. PATIENTS AND METHODS: A total of 202 patients with ovarian tumors were enrolled, including 53 with ovarian cancer, 23 with borderline malignant tumors, and 126 with benign ovarian tumors. Using 5 machine learning classifiers, including support vector machine, random forest, naive Bayes, logistic regression, and XGBoost, we derived diagnostic results from 16 features, commonly available from blood tests, patient background, and imaging tests. We also analyzed the importance of 16 features on the prediction of disease. RESULTS: The highest accuracy was 0.80 in the machine learning algorithm of XGBoost. The evaluation of importance of the features showed different results among the correlation coefficient of the features, the regression coefficient, and the features importance of random forest. CONCLUSION: AI could play a role in the prediction of pathological diagnosis of ovarian cancer from preoperative examinations.


Assuntos
Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Adolescente , Adulto , Algoritmos , Inteligência Artificial , Teorema de Bayes , Feminino , Humanos , Modelos Logísticos , Aprendizado de Máquina , Ovário/patologia , Máquina de Vetores de Suporte , Adulto Jovem
15.
Toxicol Lett ; 332: 42-55, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32629074

RESUMO

Obesity is associated with several female reproductive complications, such as polycystic ovary syndrome (PCOS). The exact mechanism of this relationship remains unclear. Few previous studies using diet containing refined carbohydrate (HCD) leading to obesity have been performed and it is unclear if HCD is linked with reproductive dysfunctions. In this investigation, we assessed whether subchronic HCD exposure results in reproductive and other irregularities. Female rats were fed with HCD for 15 days and metabolic outcomes and reproductive tract morphophysiology were assessed. We further assessed reproductive tract inflammation, oxidative stress (OS) and fibrosis. HCD rats displayed metabolic impairments, such as an increase in body weight/adiposity, adipocyte hypertrophic, abnormal lipid profile, glucose tolerance and insulin resistance (IR) and hyperleptinemia. Improper functioning of the HCD reproductive tract was observed. Specifically, irregular estrous cyclicity, high LH levels and abnormal ovarian morphology coupled with reduction in primordial and primary follicle numbers was observed, suggesting ovarian reserve depletion. Improper follicular development and a reduction in antral follicles, corpora lutea and granulosa layer area together with an increase in cystic follicles were apparent. Uterine atrophy and reduction in endometrial gland (GE) number was observed in HCD rats. Reproductive tract inflammation, OS and fibrosis were seen in HCD rats. Further, strong positive correlations were observed between body weight/adiposity and IR with estrous cycle length, cystic follicles, ovarian reserve, GE and other abnormalities. Thus, these data suggest that the subchronic HCD exposure led to PCOS-like features, impaired ovarian reserve, GE number, and other reproductive abnormalities in female rats.


Assuntos
Carboidratos da Dieta/toxicidade , Reserva Ovariana/efeitos dos fármacos , Ovário/metabolismo , Síndrome do Ovário Policístico/induzido quimicamente , Adiposidade/efeitos dos fármacos , Animais , Peso Corporal , Dieta , Ciclo Estral/efeitos dos fármacos , Feminino , Fibrose , Intolerância à Glucose/sangue , Intolerância à Glucose/induzido quimicamente , Resistência à Insulina , Leptina/sangue , Metabolismo dos Lipídeos , Folículo Ovariano/efeitos dos fármacos , Ovário/patologia , Estresse Oxidativo , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , Ratos , Ratos Wistar
16.
Eur J Clin Microbiol Infect Dis ; 39(12): 2447-2455, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32613308

RESUMO

This study compared the laboratory indexes in 40 non-severe COVID-19 patients with those in 57 healthy controls. In the peripheral blood system of non-severe symptom COVID-19 patients, lymphocytes, eosinophils, basophils, total procollagen type 1 amino-terminal propeptide, osteocalcin N-terminal, thyroid-stimulating hormone, growth hormone, and insulin-like growth factor-binding protein 3 significantly decreased, and total protein, albumin, alanine transaminase, alkaline phosphatase, γ-glutamyl transferase, activated partial thromboplastin time, prothrombin time, fibrinogen, D-dimer, fibrinogen degradation products, human epididymal protein 4, serum ferritin, and C-reactive protein were elevated. SARS-CoV-2 infection can affect hematopoiesis, hemostasis, coagulation, fibrinolysis, bone metabolism, thyroid, parathyroid glands, the liver, and the reproductive system.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Adulto , Biomarcadores/sangue , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Osso e Ossos/virologia , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Estudos Transversais , Feminino , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinólise , Hematopoese , Hemostasia , Humanos , Fígado/metabolismo , Fígado/patologia , Fígado/virologia , Masculino , Pessoa de Meia-Idade , Ovário/metabolismo , Ovário/patologia , Ovário/virologia , Glândulas Paratireoides/metabolismo , Glândulas Paratireoides/patologia , Glândulas Paratireoides/virologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/patologia , Albumina Sérica/metabolismo , Índice de Gravidade de Doença , Testículo/metabolismo , Testículo/patologia , Testículo/virologia , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Glândula Tireoide/virologia
17.
Anticancer Res ; 40(7): 4115-4121, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620660

RESUMO

BACKGROUND/AIM: Magnetic resonance (MR) and ultrasound (US) fusion imaging (MR-US fusion) is already used to guide prostate biopsies and has been proven accurate for diagnosing cervical cancer. In this study, we aimed to evaluate the feasibility and performance of MR-US fusion for characterizing adnexal masses. PATIENTS AND METHODS: A retrospective study was conducted between 2014 and 2018 including women referred to our Gynaecological Oncology Department for characterization of an adnexal mass (n=106). Performance of MR-US fusion was evaluated in a subgroup of patients who underwent surgery (n=26). Two readers, blinded to final histology, performed and rated US findings according to the International Ovarian Tumor Analysis simple rules score, MR according to Ovarian-Adnexal Reporting Data System Magnetic score, and MR-US fusion through a tailored score. The reference outcome was the final pathology. RESULTS: MR-US fusion had a sensitivity of 100% (95%CI=80-100), specificity of 89% (95%CI=52-99), positive likelihood ratio of 9 (95%CI=1.4-57), and accuracy of 96% (95%CI=80-99). CONCLUSION: MR-US fusion is feasible for characterizing adnexal masses to predict ovarian cancer.


Assuntos
Imagem por Ressonância Magnética , Neoplasias Ovarianas/diagnóstico por imagem , Ovário/diagnóstico por imagem , Ultrassonografia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Ovário/patologia , Método Simples-Cego , Adulto Jovem
18.
Adv Exp Med Biol ; 1207: 463-466, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32671768

RESUMO

Polycystic Ovary Syndrome (PCOS) is a common obesity-related reproductive disease in women of child-bearing age,which is usually accompanied with endocrine and metabolic abnormalities such as hyperandrogenemia and hyperinsulinemia. The abnormal reproductive function of PCOS is mainly characterized by the morphological and functional changes of ovary. Autophagy is involved in the maintenance of human ovarian physiological function as well as in the process of luteal degeneration, and affects the survival of granulosa cells. This chapter introduces the latest research progress of the relationship between autophagy and PCOS. How autophagy is involved in the occurrence and development of PCOS remains to be further studied.


Assuntos
Autofagia , Síndrome do Ovário Policístico , Feminino , Células da Granulosa , Humanos , Hiperandrogenismo/complicações , Hiperinsulinismo/complicações , Obesidade/complicações , Ovário/patologia , Ovário/fisiologia , Ovário/fisiopatologia , Síndrome do Ovário Policístico/complicações
19.
Medicine (Baltimore) ; 99(29): e21127, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702865

RESUMO

RATIONALE: Advanced stage ovarian cancer is rarely encountered in pregnant women, due to the high number of ultrasound imagistic studies performed during this period. The clinical course of patients diagnosed with advanced stage ovarian cancer is similar in pregnant and nonpregnant women. PATIENT CONCERNS: We present the case of a 27-year-old woman initially submitted to emergency surgery for ovarian cyst torsion in the ninth week of gestation, at that moment ovarian cystectomy being performed. DIAGNOSES: The histopathological studies demonstrated the presence of a moderately differentiated epithelial ovarian cancer. INTERVENTIONS: Although the interdisciplinary team decided for staging surgery followed by platinum-based chemotherapy beginning from the second trimester of pregnancy, both the patient and her family refused this strategy and opined for total hysterectomy en bloc with bilateral adnexectomy. Surprisingly, intraoperatively both ovaries had a tumoral aspect, whereas peritoneal carcinomatosis nodules were found in the Douglas pouch. Therefore, the neoplastic process was staged as a IIIC epithelial ovarian cancer, a total hysterectomy with bilateral adnexectomy, Douglas pouch peritonectomy, omentectomy, pelvic and para-aortic lymph node dissection being performed. OUTCOMES: The patient was discharged in the sixth postoperative day and was confined to the oncology service in order to be submitted to the standard taxanes and platinum based chemotherapy. LESSONS: Although ovarian cancer has been rarely reported during pregnancy, this diagnostic should be taken in consideration whenever persistent adnexal masses are encountered.


Assuntos
Procedimentos Cirúrgicos de Citorredução/métodos , Neoplasias Ovarianas/cirurgia , Adulto , Feminino , Humanos , Histerectomia/métodos , Linfonodos/patologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Ovariectomia/métodos , Ovário/patologia , Gravidez , Segundo Trimestre da Gravidez , Romênia
20.
Maturitas ; 137: 1-6, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32498930

RESUMO

BACKGROUND: With the significant improvement of the cure rate and survival rate of cancer patients, the survivors face quality-of-life problems, such as a significant decline in reproductive system development, ovarian reserves and function, and even fertility loss and early menopause. These problems are often highly associated with chemotherapy-induced ovarian damage in cancer treatment. However, there are no ideal treatment strategies at present. In our attempt to develop reagents and approaches for delaying ovarian aging and protecting chemotherapy-induced ovarian injury, we recently found that metformin may be the most promising drug to protect female malignant tumor patients from chemotherapy-induced ovarian injury. This trial aims to test whether administration of metformin during chemotherapy can protect the normal ovarian function of patients with early breast cancer. METHODS: This study is prospective, randomized, double-blind and placebo-controlled. Female patients with early breast cancer (N = 314) will be randomly assigned to two groups (placebo, metformin 2000 mg). Metformin will be administered during and after chemotherapy for patients with stage I-IIIa breast cancer. The primary outcome will be the menstruation recovery rate 12 months after chemotherapy, defined as recovery of menstruation twice in a row within 1 year. Patients will be followed up for 5 years to observe long-term ovarian function and prognosis, such as overall survival (OS), objective response rate (ORR), and disease-free survival (DFS). Quality of life and safety will also be assessed. DISCUSSION: Our research will provide a new treatment strategy for fertility protection, and clinical treatment guidance for cancer patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Menstruação/efeitos dos fármacos , Metformina/uso terapêutico , Ovário/efeitos dos fármacos , Adolescente , Adulto , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Pessoa de Meia-Idade , Testes de Função Ovariana , Ovário/patologia , Ovário/fisiopatologia , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica/efeitos dos fármacos , Taxa de Sobrevida , Adulto Jovem
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