38 research outputs found

    Estrogen-treated rats alter salt intake after repeated episodes of dietary sodium deficiency

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    Background: Sex differences in sodium intake are apparent; however, estrogen's role in these differences is currently unclear. Previous studies examining repeated episodes of furosemide-induced sodium depletion showed that while stimulated salt intake was similar between males and females, there were clear sex differences in sodium intake after rats were sodium replete. We aimed to further elucidate the long-term effects of estrogen on sodium intake using repeated episodes of a low salt diet, a more physiological challenge.Methods: Ovariectomized rats were placed on two-week periods of access to regular chow (NaR) or sodium deficient chow (NaD), which we alternated for a total of two exposures to each diet. Estrogen benzoate (EB) or oil injections were given twice weekly throughout the experiment. At the end of each diet period, rats were given a 2-hour two-bottle test (water and 0.5 M NaCl). At the end of the experiment, rats were sacrificed and trunk blood was collected and centrifuged to collect plasma. Plasma protein levels were measured. Uteri were collected and 1 cm segments of the uterine horns were weighed.Results: We confirmed the efficacy of EB treatment via effects on body weight, uterine weight, and plasma proteins. Specifically, EB-treated rats maintained body weight throughout the experiment, with the expected transient decreases corresponding to the EB injection schedule, while oil-treated rats gained weight. In addition, both plasma proteins and uterine weights were greatly increased in EB-treated rats compared to oil-treated rats. During two-bottle tests, both EB- and oil-treated rats had similar baseline intakes of 0.5 M NaCl and water. When salt intake was stimulated by dietary sodium deficiency, both EB- and oil-treated rats drank similarly increased amounts of 0.5 M NaCl. Interestingly, EB- treated rats drank more 0.5 M NaCl and water than did oil-treated rats following return to regular chow. The second period of dietary sodium deficiency again elicited similar intakes of 0.5 M NaCl and water by EB- and oil-treated rats.Conclusions: Our study demonstrated that estrogen did not alter salt intake induced by the physiological challenge, dietary sodium deficiency. However, the low salt diet led to persistent changes in behavior, as demonstrated by the continued consumption of salt and water by EB-treated rats even after sodium repletion

    Estrogen-Like Activity of Perfluoroalkyl Acids In Vivo and Interaction with Human and Rainbow Trout Estrogen Receptors In Vitro

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    The objectives of this study were to determine the structural characteristics of perfluoroalkyl acids (PFAAs) that confer estrogen-like activity in vivo using juvenile rainbow trout (Oncorhynchus mykiss) as an animal model and to determine whether these chemicals interact directly with the estrogen receptor (ER) using in vitro and in silico species comparison approaches. Perfluorooctanoic (PFOA), perfluorononanoic (PFNA), perfluorodecanoic (PFDA), and perfluoroundecanoic (PFUnDA) acids were all potent inducers of the estrogen-responsive biomarker protein vitellogenin (Vtg) in vivo, although at fairly high dietary exposures. A structure-activity relationship for PFAAs was observed, where eight to ten fluorinated carbons and a carboxylic acid end group were optimal for maximal Vtg induction. These in vivo findings were corroborated by in vitro mechanistic assays for trout and human ER. All PFAAs tested weakly bound to trout liver ER with half maximal inhibitory concentration (IC50) values of 15.2-289ΌM. Additionally, PFOA, PFNA, PFDA, PFUnDA, and perlfuorooctane sulfonate (PFOS) significantly enhanced human ERα-dependent transcriptional activation at concentrations ranging from 10-1000nM. Finally, we employed an in silico computational model based upon the crystal structure for the human ERα ligand-binding domain complexed with E2 to structurally investigate binding of these putative ligands to human, mouse, and trout ERα. PFOA, PFNA, PFDA, and PFOS all efficiently docked with ERα from different species and formed a hydrogen bond at residue Arg394/398/407 (human/mouse/trout) in a manner similar to the environmental estrogens bisphenol A and nonylphenol. Overall, these data support the contention that several PFAAs are weak environmental xenoestrogens of potential concer

    Estrogen-Like Activity of Perfluoroalkyl Acids In Vivo and Interaction with Human and Rainbow Trout Estrogen Receptors In Vitro

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    The objectives of this study were to determine the structural characteristics of perfluoroalkyl acids (PFAAs) that confer estrogen-like activity in vivo using juvenile rainbow trout (Oncorhynchus mykiss) as an animal model and to determine whether these chemicals interact directly with the estrogen receptor (ER) using in vitro and in silico species comparison approaches. Perfluorooctanoic (PFOA), perfluorononanoic (PFNA), perfluorodecanoic (PFDA), and perfluoroundecanoic (PFUnDA) acids were all potent inducers of the estrogen-responsive biomarker protein vitellogenin (Vtg) in vivo, although at fairly high dietary exposures. A structure-activity relationship for PFAAs was observed, where eight to ten fluorinated carbons and a carboxylic acid end group were optimal for maximal Vtg induction. These in vivo findings were corroborated by in vitro mechanistic assays for trout and human ER. All PFAAs tested weakly bound to trout liver ER with half maximal inhibitory concentration (IC50) values of 15.2–289ÎŒM. Additionally, PFOA, PFNA, PFDA, PFUnDA, and perlfuorooctane sulfonate (PFOS) significantly enhanced human ERα-dependent transcriptional activation at concentrations ranging from 10–1000nM. Finally, we employed an in silico computational model based upon the crystal structure for the human ERα ligand-binding domain complexed with E2 to structurally investigate binding of these putative ligands to human, mouse, and trout ERα. PFOA, PFNA, PFDA, and PFOS all efficiently docked with ERα from different species and formed a hydrogen bond at residue Arg394/398/407 (human/mouse/trout) in a manner similar to the environmental estrogens bisphenol A and nonylphenol. Overall, these data support the contention that several PFAAs are weak environmental xenoestrogens of potential concern

    Volumetric tumor growth rates of meningiomas involving the intracranial venous sinuses

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    Object: There is currently no consensus as to whether meningiomas located inside the venous sinuses should be aggressively or conservatively treated. The goals of this study were to identify how sinus-invading meningiomas grow, report and compare growth rates of tumor components inside and outside the different venous sinuses, identify risk factors associated with increased tumor growth, and determine the effects of the extent of tumor resection on recurrence for meningiomas that invade the dural venous sinuses. Methods: Adult patients who underwent primary, non-biopsy resection of a WHO grade 1 meningioma invading the dural venous sinuses at a tertiary care institution between 2007 and 2015 were retrospectively reviewed. Rates of tumor growth were fit to several growth models to evaluate the most accurate model. Cohen’s d analysis was used to identify associations with increased growth of tumor in the venous sinuses. Logistic regression was used to compare extent of resection with recurrence. Results: Of the 68 patients included in the study, 34 patients had postoperative residual tumors in the venous sinuses that were measured over time. The growth model that best fit the growth of intrasinus meningiomas was the Gompertzian growth model (r2 = 0.93). The annual growth rate of meningiomas inside the sinuses was 7.3%, compared to extrasinus tumors with 13.6% growth per year. The only factor significantly associated with increased tumor growth in sinuses was preoperative embolization (effect sizes (ES) [95% CI], 1.874 [7.633–46.735], p = 0.008). Conclusions: This study shows that meningiomas involving the venous sinuses have a Gompertzian-type growth with early exponential growth followed by a slower growth rate that plateaus when they reach a certain size. Overall, the growth rate of the intrasinus portion is low (7.3%), which is half of the reported growth rates for other studies involving primarily extrasinus tumors

    Extending the resection beyond the contrast-enhancement for glioblastoma: feasibility, efficacy, and outcomes

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    Object: It is becoming well-established that increasing extent of resection with decreasing residual volume is associated with delayed recurrence and prolonged survival for patients with glioblastoma (GBM). These prior studies are based on evaluating the contrast-enhancing (CE) tumour and not the surrounding fluid attenuated inversion recovery (FLAIR) volume. It therefore remains unclear if the resection beyond the CE portion of the tumour if it translates into improved outcomes for patients with GBM. Methods: Adult patients who underwent resection of a primary glioblastoma at a tertiary care institution between January 1, 2007 and December 31, 2012 and underwent radiation and temozolomide chemotherapy were retrospectively reviewed. Pre and postoperative MRI images were measured for CE tumour and FLAIR volumes. Multivariate proportional hazards were used to assess associations with both time to recurrence and death. Values with p < 0.05 were considered statistically significant. Results: 245 patients met the inclusion criteria. The median [IQR] preoperative CE and FLAIR tumour volumes were 31.9 [13.9–56.1] cm3 and 78.3 [44.7–115.6] cm3, respectively. Following surgery, the median [IQR] postoperative CE and FLAIR tumour volumes were 1.9 [0–7.1] cm3 and 59.7 [29.7–94.2] cm3, respectively. In multivariate analyses, the postoperative FLAIR volume was not associated with recurrence and/or survival (p > 0.05). However, the postoperative CE tumour volume was significantly associated with both recurrence [HR (95%CI); 1.026 (1.005–1.048), p= 0.01] and survival [HR (95%CI); 1.027 (1.007–1.032), p= 0.001]. The postoperative FLAIR volume was also not associated with recurrence and/or survival among patients who underwent gross total resection of the CE portion of the tumour as well as those who underwent supratotal resection. Conclusions: In this study, the volume of CE tumour remaining after resection is more important than FLAIR volume in regards to recurrence and survival for patients with GBM
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