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Previous studies have suggested that the effects of androgens on body weight (BW) and appetite are affected by the estrogen milieu in females; however, the mechanism underlying these effects remains unclear. We hypothesized that androgens may affect endogenous oxytocin (OT), which is a hypothalamic anorectic factor, and that these effects of androgens may be altered by the estrogen milieu in females. To investigate this hypothesis, in the present study, we examined the effects of testosterone on peripheral and central OT levels in ovariectomized female rats that did or did not receive estradiol supplementation. Ovariectomized female rats were randomly divided into non-estradiol-supplemented or estradiol-supplemented groups, and half of the rats in each group were concurrently supplemented with testosterone (i.e., rats were divided into four groups, n = 7 per each group). We also measured peripheral and central OT receptor (OTR) gene expression levels. As a result, we found that testosterone increased serum and hypothalamic OT levels and OT receptor mRNA levels in non-estradiol-supplemented rats, whereas it had no effects on these factors in estradiol-supplemented rats. In addition, testosterone reduced food intake, BW gain, and fat weight in non-estradiol-supplemented rats, whereas it did not have any effects on BW, appetite, or fat weight in estradiol-supplemented rats. These findings indicate that the effects of androgens on OT may be affected by the estrogen milieu, and elevated OT levels may be related to the blunting of appetite and prevention of obesity under estrogen-deficient conditions.
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Estradiol , Hipotálamo , Ovariectomia , Ocitocina , Receptores de Ocitocina , Testosterona , Animais , Ocitocina/sangue , Ocitocina/farmacologia , Feminino , Testosterona/sangue , Hipotálamo/metabolismo , Hipotálamo/efeitos dos fármacos , Estradiol/sangue , Estradiol/farmacologia , Ratos , Receptores de Ocitocina/metabolismo , Receptores de Ocitocina/genética , Estrogênios/sangue , Estrogênios/farmacologia , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Ratos Sprague-Dawley , Apetite/efeitos dos fármacos , RNA Mensageiro/metabolismoRESUMO
Objectives: Before endometriosis surgery, it is important to identify deep infiltrating endometriosis (DIE) to assess the surgical difficulty. Preoperative magnetic resonance imaging (MRI) was used to determine which findings are useful in predicting DIE. Materials and Methods: Between 2008 and 2016, 54 patients with adenomyosis underwent total laparoscopic hysterectomy at our hospital. We retrospectively evaluated the intraoperative findings and magnetic resonance imaging (MR) images. The MR images were scored based on the presence of five findings: retroflexed uterus, elevated posterior vaginal fornix, intestinal tethering in the direction of the uterus, faint strands between the uterus and intestine, and fibrotic nodules covering the serosal surface of the uterus. Results: Of the five findings, intestinal tethering and faint strands between the uterus and intestine showed a sensitivity of 73% and a specificity of 91%-100%, indicating the usefulness of these findings for detecting deep endometriosis lesions. However, finding a retroflexed uterus did not contribute to DIE lesion detection. The sensitivities of an elevated posterior fornix and fibrotic nodules covering the surface of the uterus were as low as 46%-59%, and their specificities were as high as 84%-91%. Conclusion: Preoperative preparation is essential for patients with intestinal tethering or faint strands between the uterus and intestine on preoperative MRI after obtaining appropriate informed consent.
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PURPOSE: The challenges of fertility loss owing to cancer treatment persist long after treatment. However, psychosocial care for fertility among cancer survivors who have completed cancer treatment is insufficient. This systematic review examined psychosocial experiences related to the potential loss of fertility and unsuccessful pregnancy after treatment in cancer survivors of reproductive age to identify psychosocial care needs. METHODS: A systematic review was conducted using the online databases PubMed, Cochrane Library, PsycINFO, CINAHL, and Ichushi-Web between August and December 2022 to identify studies that addressed psychosocial experiences after fertility loss or failure to conceive among young cancer survivors. Study quality was assessed using the Mixed Methods Appraisal Tool. RESULTS: Forty studies were included, revealing psychosocial experiences across five categories: subjective fear of (potential) fertility loss, impact on romantic relationships, alternative methods for family building, reliance on social support, and specialized care. Only one study addressed the psychosocial aspects after complete loss of fertility in young cancer survivors. CONCLUSIONS: The possibility and uncertainty of fertility loss led to stress and depression, loss of identity, decreased opportunities to meet a new partner, and damaged relationships established before diagnosis. The needs encompass fertility preservation, sexuality, approaches to building a family, partner communication, and other diverse needs.
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Sobreviventes de Câncer , Humanos , Sobreviventes de Câncer/psicologia , Feminino , Gravidez , Apoio Social , Neoplasias/psicologia , Neoplasias/complicações , Neoplasias/terapia , Preservação da Fertilidade/métodos , Preservação da Fertilidade/psicologiaRESUMO
PURPOSE: Inherited cancer susceptibility is often not suspected in the absence of a significant cancer family history. Pathogenic germline variants in pancreatic cancer are well-studied, and routine genetic testing is recommended in the guidelines. However, data on rare periampullary cancers other than pancreatic cancer are insufficient. We compared the prevalence of germline susceptibility variants in patients with pancreatic cancer and nonpancreatic periampullary cancers. MATERIALS AND METHODS: Six hundred and eight patients who had undergone pancreaticoduodenal resection at a tertiary referral hospital were studied, including 213 with pancreatic ductal adenocarcinoma, 172 with ampullary cancer, 154 with distal common bile duct cancer, and 69 with duodenal adenocarcinoma. Twenty cancer susceptibility and candidate susceptibility genes were sequenced, and variant interpretation was assessed by interrogating ClinVar and PubMed. RESULTS: Pathogenic or likely pathogenic, moderate- to high-penetrant germline variants were identified in 46 patients (7.7%), including a similar percentage of patients with pancreatic (8.5%) and nonpancreatic periampullary cancer (7.1%). Low-penetrant variants were identified in an additional 11 patients (1.8%). Eighty-nine percent of the moderate- to high-penetrant variants involved the major cancer susceptibility genes BRCA2, ATM, BRCA1, CDKN2A, MSH2/MLH1, and PALB2; the remaining 11% involved other cancer susceptibility genes such as BRIP1, BAP1, and MSH6. Almost all pathogenic variant carriers had a family history of cancer. CONCLUSION: Patients with pancreatic and nonpancreatic periampullary cancer have a similar prevalence of pathogenic cancer susceptibility variants. Germline susceptibility testing should be considered for patients with any periampullary cancer.
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Ampola Hepatopancreática , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/genética , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Ampola Hepatopancreática/patologia , Adulto , Neoplasias do Ducto Colédoco/genética , Idoso de 80 Anos ou mais , Neoplasias Duodenais/genética , Neoplasias Duodenais/patologiaRESUMO
Kisspeptin is a peptide that plays an important role through its effects on the hypothalamus-pituitary-gonadal (HPG) axis. It has also been implicated in sexual behavior. The present study investigated whether the relationship between kisspeptin and sexual behavior is independent of the HPG axis, i.e., testosterone. Sexual behavior was examined after the administration of kisspeptin to gonadally intact male rats and gonadectomized male rats that received testosterone supplementation. Other male rats were also observed for sexual behavior once a week from 2 to 5 weeks after gonadectomy and receiving kisspeptin for the sixth postoperative week. Sexual behavior in female rats serving as the partner for each male was also observed. Female rats were not administered kisspeptin in the present study. The results obtained showed that the administration of kisspeptin increased precopulatory behavior in gonadally intact male rats and gonadectomized male rats that received testosterone supplementation and proceptive behavior in their female partners. Precopulatory behavior in males and receptive behavior in females increased, while copulatory behavior in males and receptive behavior in females remained unchanged. Furthermore, the administration of kisspeptin increased precopulatory behavior in gonadectomized males, but did not affect receptive behavior in females. These results suggest that kisspeptin affected males independently and/or supplementally to testosterone, and also that changes in the presence of testosterone in males had an impact on proceptive behavior in their female partners. In conclusion, kisspeptin may involve an as-yet-unidentified neural pathway in sexual desire independently of the HPG axis.
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Kisspeptinas , Comportamento Sexual Animal , Testosterona , Animais , Kisspeptinas/metabolismo , Kisspeptinas/farmacologia , Masculino , Testosterona/farmacologia , Feminino , Ratos , Comportamento Sexual Animal/efeitos dos fármacos , Comportamento Sexual Animal/fisiologia , Ratos Wistar , Copulação/efeitos dos fármacos , Copulação/fisiologiaRESUMO
Secreted frizzled-related proteins (SFRPs) are involved in the development of various types of cancer and function by suppressing the Wnt signaling pathway. To elucidate the clinical implications of SFRPs in uterine sarcoma, SFRP expression levels and their effects on uterine leiomyosarcoma cells were examined. Immunostaining for SFRP4 was performed on uterine smooth muscle, uterine fibroid and uterine leiomyosarcoma tissues. Additionally, the effects of SFRP4 administration on cell viability, migration and adhesion were evaluated in uterine leiomyosarcoma SKN cells using the WST-1 assay (Roche Diagnostics) and the CytoSelect™ 24-well Cell Migration Assay Kit and the CytoSelect™ 48-well Cell Adhesion Assay Kit. The expression levels of SFRP4 in uterine leiomyosarcoma tissues were lower than those in normal smooth muscle and uterine fibroid tissues. In addition, SFRP4 suppressed the viability and migration, and increased the adhesion ability of uterine leiomyosarcoma cells compared with in the control group. In conclusion, SFRP4 may suppress the viability and migration, and enhance the adhesion of sarcoma cells. These results suggested that SFRP4 could be considered as a novel therapeutic target for uterine sarcoma.
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Polycystic ovary syndrome (PCOS) is associated with an increased risk of psychological distress as well as enhanced responses to psychosocial stress. Recently, it was hypothesized that PCOS patients may be at high risk of novel COVID-19 infections and worse clinical presentations during such infections. Here, we evaluated the effects of PCOS on stress responses to bacterial and viral mimetics using dihydrotestosterone-induced PCOS model rats. Lipopolysaccharide (LPS; a bacterial mimetic) or polyinosinic-polycytidylic acid (Poly-IC; a viral mimetic) was injected into PCOS model rats (PCOS) and non-PCOS rats (control), and the rats' stress responses were evaluated. In the PCOS group, the rats' anorectic and febrile responses to LPS injection were enhanced, whereas their anorectic and febrile responses to Poly-IC injection were unaltered. The PCOS group also exhibited greater changes in peripheral cytokine levels in response to LPS, but not Poly-IC. On the contrary, after the injection of Poly-IC depressed locomotor activity was more evident in the PCOS group, whereas no such changes were observed after LPS injection. These findings indicate that although the stress responses of PCOS model rats to infection may be enhanced, the patterns of change in stress responses and their underlying mechanisms may differ between bacterial and viral infections.
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PURPOSE: Circulating carbohydrate antigen 19-9 (CA19-9) levels reflect FUT3 and FUT2 fucosyltransferase activity. Measuring the related glycan, DUPAN-2, can be useful in individuals unable to synthesize CA19-9. We hypothesized that similar to CA19-9, FUT functional groups determined by variants in FUT3 and FUT2 influence DUPAN-2 levels, and having tumor marker reference ranges for each functional group would improve diagnostic performance. MATERIALS AND METHODS: Using a training/validation study design, FUT2/FUT3 genotypes were determined in 938 individuals from Johns Hopkins Hospital: 607 Cancer of the Pancreas Screening (CAPS) study subjects with unremarkable pancreata and 331 with pancreatic ductal adenocarcinoma (PDAC). Serum DUPAN-2 and CA19-9 levels were measured by immunoassay. RESULTS: In controls, three functional FUT groups were identified with significant differences in DUPAN-2 levels: FUT3-intact, FUT3-null/FUT2-intact, and FUT3-null/FUT2-null. DUPAN-2 training set diagnostic cutoffs for each FUT group yielded higher diagnostic sensitivity in the validation set for patients with stage I/II PDAC than uniform cutoffs (60.4% [95% CI, 50.2 to 70.0] v 39.8% [30.0 to 49.8]), at approximately 99% (96.7 to 99.6) specificity. Combining FUT/CA19-9 and FUT/DUPAN-2 tests yielded 78.4% (72.3 to 83.7) sensitivity for stage I/II PDAC, at 97.7% (95.3 to 99.1) specificity in the combined sets, with higher AUC (stage I/II: 0.960 v 0.935 for CA19-9 + DUPAN-2 without the FUT test; P < .001); for stage I PDAC, sensitivity was 62.0% (49.1 to 73.2; AUC, 0.919 v 0.883; P = .03). CA19-9 levels in FUT3-null/FUT2-null PDAC subjects were higher than in FUT3-null/FUT2-intact subjects (median/IQR; 24.9/57.4 v <1/2.3 U/mL; P = .0044). In a simulated CAPS cohort, AUC precision recall (AUCPR) scores were 0.51 for CA19-9 alone, 0.64 for FUT/CA19-9, 0.73 for CA19-9/DUPAN-2, and 0.84 for FUT/CA19-9/DUPAN-2. CONCLUSION: Using a tumor marker gene test to individualize CA19-9 and DUPAN-2 reference ranges achieves high diagnostic performance for stage I/II pancreatic cancer.
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Biomarcadores Tumorais , Antígeno CA-19-9 , Carcinoma Ductal Pancreático , Fucosiltransferases , Galactosídeo 2-alfa-L-Fucosiltransferase , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/sangue , Fucosiltransferases/genética , Antígeno CA-19-9/sangue , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Pessoa de Meia-Idade , Feminino , Masculino , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/diagnóstico , Idoso , Genótipo , Sensibilidade e Especificidade , Antígenos de NeoplasiasRESUMO
Objectives: Surgery for pregnant women with ovarian tumors poses the risk of uterine irritation. We aimed to demonstrate the superiority of our laparoscopic technique over conventional methods and to compare the outcomes of laparoscopy with those of laparotomy for ovarian tumors during pregnancy. Materials and Methods: This retrospective study included 50 patients undergoing procedures for ovarian tumors during pregnancy at the Tokushima University Hospital between January 2005 and December 2021. We compared surgical outcomes between laparoscopic procedures and laparotomy, along with complications. In addition, we compared the frequency of uterine stimulation with the conventional trocar position to that with the currently used trocar position in laparoscopic surgery. Results: Forty patients in the laparoscopy group and 10 in the laparotomy group underwent procedures. The laparoscopy group had less bleeding (16.4 ± 28.8 vs. 58 ± 72.2 mL, P < 0.05) and shorter hospital stays (7.6 ± 1.7 vs. 12.8 ± 13.1 days, P < 0.05) compared with those of the laparotomy group. The outcomes showed no significant differences between groups. All laparoscopies and laparotomies were successful and without complications. Furthermore, the current trocar position tended to stimulate the uterus less frequently. Conclusion: The results suggested that, compared to laparotomy, laparoscopy for ovarian tumors during pregnancy had better outcomes. The trocar position in our technique allows for easy operation of ovarian tumors without interference by forceps or cameras, resulting in minimal irritation of the uterus. Our original laparoscopic method may be safer with superior outcomes over the conventional method.
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BACKGROUND: Cancer antigen 19-9 (CA19-9) is widely used as a marker of pancreatic cancer tumor burden and response to therapy. Synthesis of CA19-9 and its circulating levels are determined by variants encoding the fucosyltransferases, FUT2 and FUT3. Individuals can be grouped into one of four functional FUT groups (FUT3-null, FUT-low, FUT-intermediate, FUT-high), each with its own CA19-9 reference range based on its predicted capacity to produce CA19-9. The authors hypothesized that a FUT variant-based CA19-9 tumor marker gene test could improve the prognostic performance of CA19-9. METHODS: Preoperative and pre-treatment CA19-9 levels were measured, and FUT variants were determined in 449 patients who underwent surgery for pancreatic ductal adenocarcinoma (PDAC) at Johns Hopkins Hospital between 2010 and 2020, including 270 patients who underwent neoadjuvant therapy. Factors associated with recurrence-free and overall survival were determined in Cox proportional hazards models. RESULTS: Higher preoperative CA19-9 levels were associated with recurrence and mortality for patients in the higher-FUT groups (FUT-intermediate, FUT-high for mortality, with adjustment for other prognostic factors; hazard ratio [HR], 1.34 and 1.58, respectively; P < 0.001), but not for those in the lower-FUT groups (FUT3-null, FUT-low). As a tumor marker, CA19-9 levels of 100 U/ml or lower after neoadjuvant therapy and normalization of CA19-9 based on FUT group were more sensitive but less specific predictors of evidence for a major pathologic response to therapy (little/no residual tumor) and of early recurrence (within 6 months). CONCLUSION: Among patients undergoing pancreatic cancer resection, a CA19-9 tumor marker gene test modestly improved the prognostic performance of CA19-9.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Antígeno CA-19-9 , Biomarcadores Tumorais/genética , Estudos Retrospectivos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/cirurgia , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/cirurgia , PrognósticoRESUMO
Activin A promotes the development of endometriotic lesions in a murine model of endometriosis, and the immunohistochemical localization of phosphorylated suppressor of mothers against decapentaplegic homolog 2/3 (pSMAD2/3) complex in endometriotic lesions has been reported. Activin may therefore be involved in the development and proliferation of endometriotic cells via the SMAD signaling pathway. However, few detailed reports exist on SMAD7 expression in endometriosis. The purpose of this study was to investigate the expression of pSMAD2/3 or pSMAD3 and SMAD7 in the orthotopic human endometrium, ovarian endometriosis, and endometriotic lesions in a murine model and the effect of activin A on pSMAD2/3 and SMAD7 expression. We established an endometriosis murine model via the intraperitoneal administration of endometrial tissue and blood from donor mice. Activin A was intraperitoneally administered to the activin group. We immunohistochemically evaluated orthotopic endometria, ovarian endometriotic tissues, and endometriotic lesions in the murine model followed by western blotting. We found that pSMAD3 and SMAD7 were expressed in ovarian endometriosis and orthotopic endometria from patients with and without endometriosis. In the murine model, endometriotic lesions expressed pSMAD2/3 and SMAD7 in the activin and control groups, and higher SMAD7 expression was found in the activin group. To the best of our knowledge, this study is the first to show that SMAD7 expression is upregulated in endometriosis. In conclusion, these results suggest that activin A activates the SMAD signaling pathway and promotes the development of endometriotic lesions, thus identifying SMAD7 as a potential therapeutic target for endometriosis.
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Ativinas , Modelos Animais de Doenças , Endometriose , Endométrio , Proteína Smad2 , Proteína Smad3 , Proteína Smad7 , Endometriose/metabolismo , Endometriose/patologia , Feminino , Animais , Humanos , Endométrio/metabolismo , Endométrio/patologia , Camundongos , Proteína Smad7/metabolismo , Proteína Smad3/metabolismo , Proteína Smad2/metabolismo , Ativinas/metabolismo , Doenças Ovarianas/metabolismo , Doenças Ovarianas/patologia , Adulto , Transdução de SinaisRESUMO
Here we report a comparative study on the bottom-up synthesis of multi-element hydroxides composed of Mg, Al, Fe and Zn cations to understand the role of solvents. Two common solvents, water and ethylene glycol, a typical polyol, are used. The polyol-derived MgAlFeZn-OH are nanosheets with homogeneous elemental distribution, while the hydrothermal-derived MgAlFeZn-OH are mixtures of plate-like hydroxide layers and rod-like spinel oxides. The coordinating properties and the high viscosity of the ethylene glycol provide the possibility to mediate the hydrolysis rates and to control the particle growth. The high specific surface area of the polyol-derived multi-element hydroxide nanosheets (352.4 m2 g-1) guarantees them as excellent adsorbents for adsorbing anionic dyes in aqueous solution.
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While the effects of progesterone on body weight and appetite in pre-menopausal conditions have been well elucidated, its effects in post-menopausal conditions have not been clarified. On the contrary, the effects of estrogen on body weight and appetite in post-menopausal conditions have been well established. In this study, the effects of progesterone treatment on body weight, appetite, and fat mass in ovariectomized rats were evaluated. In addition, the central and/or peripheral levels of oxytocin (OT), leptin, and their receptors, which are potent anorectic factors, were examined. Female rats were ovariectomized and divided into control, progesterone-treated, and estrogen-treated groups. Body weight, food intake, and subcutaneous fat mass were lower in both the progesterone and estrogen groups than in the control group. The estrogen group exhibited higher serum OT levels than the control group, whereas the OT levels of the progesterone and control groups did not differ. The serum leptin levels of both the progesterone and estrogen groups were lower than those of the control group. Gene expression analysis of OT, leptin, and their receptors in the hypothalamus and adipose tissue found few significant differences among the groups. Hypothalamic neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) mRNA levels involved in appetite regulation were slightly altered in the progesterone and estrogen groups. These findings suggest that progesterone treatment may have favorable effects on body weight, appetite, and fat mass regulation in post-menopausal conditions and that the mechanisms underlying these effects of progesterone differ from those underlying the effects of estrogen.
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Leptina , Progesterona , Ratos , Animais , Feminino , Leptina/metabolismo , Progesterona/farmacologia , Progesterona/metabolismo , Ingestão de Alimentos , Peso Corporal , Hipotálamo , Proteínas de Transporte , Estrogênios/farmacologia , Estrogênios/metabolismo , Pró-Opiomelanocortina/genética , Pró-Opiomelanocortina/metabolismo , Pró-Opiomelanocortina/farmacologiaRESUMO
Purpose: The purpose of this study was to examine the association between fertility issues and demographic characteristics of unmarried adolescent and young adult cancer survivors. Methods: We conducted a survey among cancer survivors who were 15-39 years old and unmarried at the time of cancer diagnosis and 20-45 years old at the time of the survey. Views on fertility issues, originally developed based on the results of a qualitative study conducted with the same inclusion criteria, were used to assess thoughts and feelings regarding fertility issues. Results: Through exploratory factor analysis of the 128 respondents who either had children or desired children, two factors related to fertility issues were identified: "anxiety related to the possibility of not being able to have children" and "pressure from others to have children." Multiple regression analysis was performed to examine the association between these factors and demographic characteristics. The analysis revealed that being male and having a partner were significant predictors for both factors for views on fertility issues. Additionally, younger age at the time of diagnosis was a significant predictor for the first factor. Conclusions: Greater fertility issues among unmarried cancer survivors were associated with younger age at diagnosis, having a partner, and being male. Surprisingly, contrary to previous findings, male cancer survivors experienced more significant fertility problems than women. This result may be attributed to the well-established gender roles in Japan, where men are predominantly considered the heirs and inheritors of the family.
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Sobreviventes de Câncer , Infertilidade , Neoplasias , Criança , Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa Solteira , Infertilidade/psicologia , Emoções , Fertilidade , Neoplasias/complicações , Neoplasias/psicologiaRESUMO
In recent years, the effects of androgens on metabolic and body weight regulation systems and their underlying mechanisms have been gradually revealed in females. In women and experimental animals of reproductive age, androgen excess can adversely affect metabolic functioning, appetite, and body weight regulation. In addition, excess androgens can increase the risk of metabolic disorders, such as obesity, insulin resistance, and diabetes. These unfavorable effects of androgens are induced by alterations in the actions of hypothalamic appetite-regulatory factors, reductions in energy expenditure, insulin resistance in skeletal muscle, and ß-cell dysfunction. Interestingly, these unfavorable effects of androgens on metabolic and body-weight regulation systems are neither observed nor evident in ovariectomized animals and post-menopausal women, indicating that the adverse effects of androgens might be dependent on the estrogen milieu. Recent findings may provide novel sex- and age-specific strategies for treating metabolic diseases.
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Resistência à Insulina , Doenças Metabólicas , Síndrome do Ovário Policístico , Animais , Humanos , Feminino , Androgênios/farmacologia , Androgênios/metabolismo , Resistência à Insulina/fisiologia , Obesidade/metabolismo , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Animais de Laboratório/metabolismo , Síndrome do Ovário Policístico/metabolismoRESUMO
OBJECTIVE: The effects of oocyte activation with a Ca ionophore and roscovitine (Ca+R), a selective inhibitor of M-phase promoting factor, on unfertilized oocytes after intracytoplasmic sperm injection (ICSI) or testicular sperm extraction (TESE)-ICSI were evaluated. METHOD: Oocytes without pronuclei at 18 hours after ICSI were judged to be unfertilized and were exposed to the Ca ionophore A23187 (5 ?M) with or without roscovitine (50 ?M). The activation rate was measured 3, 7, and 18 hours later. Oocytes with two polar bodies and two pronuclei with a sperm tail were judged to have been activated. RESULTS: At 18 hours, the activation rates in the control, Ca ionophore, and Ca+R groups were 3.5% (4/112), 26.9% (7/26), and 32.1% (17/53), respectively. The activation rate of the Ca+R group was significantly higher than that of the control and similar to that of the Ca ionophore group. Among the oocytes that remained unfertilized after TESE-ICSI, the activation rates of the Ca ionophore and Ca+R groups were 22.2% (2/9) and 43.8% (7/16), respectively. CONCLUSIONS: Sequential treatment with an Ca ionophore and roscovitine activates oocytes that remain unfertilized after ICSI. In TESE-ICSI, the activation rate tended to be increased by the co-administration of roscovitine with a Ca ionophore. J. Med. Invest. 70 : 321-324, August, 2023.
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Sêmen , Injeções de Esperma Intracitoplásmicas , Humanos , Masculino , Ionóforos/farmacologia , Roscovitina/farmacologia , Oócitos/fisiologiaRESUMO
INTRODUCTION: Obstructed hemivagina and ipsilateral renal agenesis (OHVIRA) is a rare urogenital malformation. The clinical symptoms of OHVIRA include uterine morphology abnormality, persistent vaginal discharge, and renal anomaly or agenesis. Delayed diagnosis can lead to complications, such as pelvic inflammatory disease, adhesion to the oviduct, and endometriosis. PRESENTATION OF CASE: We report the case of a 12-year-old girl who presented with severe dysmenorrhea and abnormal vaginal discharge. The patient was diagnosed with OHVIRA based on magnetic resonance imaging findings. The patient underwent combined transvaginal and laparoscopic surgery for drainage of hematocolpos and adhesiolysis of the pelvic cavity. The patient had an uncomplicated recovery and normal menstrual cycle after surgery. DISCUSSION: OHVIRA is a rare syndrome, of which delayed diagnosis may result in the development of endometriosis. CONCLUSION: We report that a combined laparoscopic and transvaginal approach was useful for treating OHVIRA with oviductal hematoma.
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INTRODUCTION: Associations of luteinizing hormone (LH) with androgens during the menopausal transition and associations between follicle-stimulating hormone (FSH) levels and various diseases related to reproductive hormones in postmenopause have received much attention. LH and FSH are also known to be associated with activities of enzymes related to reproductive hormones. We examined the associations of LH and FSH with androgens and estrogens in each stage of the menopausal transition according to a classification from menopausal transition to postmenopause. METHODS: This study was a cross-sectional design. We basically used the Stage of Reproductive Aging Workshop (STRAW) + 10. We divided the 173 subjects into 6 groups according to menstrual regularity and follicle-stimulating hormone level: mid reproductive stage (Group A), late reproductive stage (Group B), early menopausal transition (Group C), late menopausal transition (Group D), very early postmenopause (Group E) and early postmenopause (Group F). Levels of LH, FSH, dehydroepiandrosterone sulfate (DHEAS), estradiol, estrone, testosterone (T), free T, androstenedione and androstenediol were measured. RESULTS: In Group A, LH showed significant positive correlations with androstenedione and estrone. In Group D, LH was positively associated with T and free T and was negatively associated with estradiol. In Groups B, C, D and F, LH showed significant positive correlations with FSH, and there was a tendency for an association between LH and FSH in Group E. FSH was associated with estradiol but not with estrone in Groups C and D. CONCLUSION: The associations of LH and FSH with reproductive hormones are different depending on the stage of the menopausal transition. TRIAL REGISTRATION: Trial registration number 2356-1; Date of registration: 18/02/2018, retrospectively registered.
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Androstenodiona , Estrona , Feminino , Humanos , Hormônio Foliculoestimulante , Estudos Transversais , Hormônio Luteinizante , Menopausa , Estradiol , Androgênios , TestosteronaRESUMO
Sex steroid hormones are important for the maintenance of metabolism in both sexes. Oxytocin (OT) is a neuropeptide that is synthesized in hypothalamic regions, secreted from the posterior lobe of the pituitary gland, and is involved in the control of appetite, body weight, and metabolism. Estrogen and OT both play a role in the metabolism of nutrients, and OT has potential in the prevention of obesity. However, the relationship between testosterone and OT remains unclear. Therefore, the present study investigated the relationship between testosterone and OT in hypogonadal male rats and male rats receiving testosterone replacement therapy. The results obtained showed that testosterone increased serum OT levels and promoted the secretion of adiponectin from visceral fat, and reduced body fat directly and/or indirectly through OT and adiponectin. Testosterone also increased the expression of OT receptors in the hypothalamus to increase sensitivity to OT, and perhaps because of this, OT administration had the effect of reducing food intake and body weight gain in both normal and castrated rats, and this effect was stronger in normal rats. In other words, the preventative effects of OT on obesity may be synergistic with testosterone. Collectively, the present results indicate that testosterone exerts indirect effects to prevent obesity and atherosclerosis through OT and adiponectin. In conclusion, testosterone replacement therapy is useful for preventing obesity caused by hypogonadism, and OT has potential in supportive medicine to prevent obesity and adult diseases.
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Ocitocina , Testosterona , Feminino , Ratos , Animais , Masculino , Ocitocina/farmacologia , Ocitocina/uso terapêutico , Testosterona/farmacologia , Adiponectina , Obesidade/prevenção & controle , Obesidade/etiologia , Peso CorporalRESUMO
To improve synthetic media for protein expression in Escherichia coli, a strategy using deep neural networks (DNN) and Bayesian optimization was performed in this study. To obtain training data for a deep learning algorithm, E. coli harvesting a plasmid pRSET/emGFP, which introduces the green fluorescence protein (GFP), was cultivated in 81 media designed using a Latin square in deepwell-scale cultivation. The media were composed of 31 components with three levels. The resultant GFP fluorescence intensities were evaluated using a fluorescence spectrometer, and the intensities were in the range 2.69-7.99 × 103. A deep neural network model was used to estimate the GFP fluorescence intensities from the culture media compositions, and accuracy was evaluated using cross-validation with 15% test data. Bayesian optimization using the best DNN model was used to calculate 20 representative compositions optimized for GFP expression. According to the validating cultivation, the simulated GFP expression levels included large errors between the estimated and experimental data. The DNN model was retrained using data from the validating cultivation, and secondary estimations were performed. The secondary estimations fit the corresponding experimental data well, and the best GFP fluorescence intensity was 1.4-fold larger than the best of the initial test composition.