Knowledge of possible toxic mechanisms (or modes) of action (MOA) of chemicals can provide valuable insights as to appropriate methods for assessing exposure and effects, thereby reducing ...uncertainties related to extrapolation across species, endpoints and chemical structure. However, MOA-based testing seldom has been used for assessing the ecological risk of chemicals. This is in part because past regulatory mandates have focused more on adverse effects of chemicals (reductions in survival, growth or reproduction) than the pathways through which these effects are elicited. A recent departure from this involves endocrine-disrupting chemicals (EDCs), where there is a need to understand both MOA and adverse outcomes. To achieve this understanding, advances in predictive approaches are required whereby mechanistic changes caused by chemicals at the molecular level can be translated into apical responses meaningful to ecological risk assessment. In this paper we provide an overview and illustrative results from a large, integrated project that assesses the effects of EDCs on two small fish models, the fathead minnow (
Pimephales promelas) and zebrafish (
Danio rerio). For this work a systems-based approach is being used to delineate toxicity pathways for 12 model EDCs with different known or hypothesized toxic MOA. The studies employ a combination of state-of-the-art genomic (transcriptomic, proteomic, metabolomic), bioinformatic and modeling approaches, in conjunction with whole animal testing, to develop response linkages across biological levels of organization. This understanding forms the basis for predictive approaches for species, endpoint and chemical extrapolation. Although our project is focused specifically on EDCs in fish, we believe that the basic conceptual approach has utility for systematically assessing exposure and effects of chemicals with other MOA across a variety of biological systems.
Purpose
Peritoneal carcinomatosis or pseudomyxoma peritonei from urachus is a rare form of presentation, often diagnosed at an advanced state of tumor burden. Because of its rarity, little is known ...about its natural history, prognosis, or optimal treatment. We searched a large international multicenter database of peritoneal surface disease to identify cases of peritoneal carcinomatosis of urachus that were treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) at expert centers. The aim is to improve knowledge and understanding of the disease and standardize its treatment.
Methods
A prospective multicenter international database was retrospectively searched to identify all patients with urachus tumor and peritoneal metastases who underwent CRS and HIPEC through the Peritoneal Surface Oncology Group International (PSOGI). Postoperative complications, long-term results, and principal prognostic factors were analyzed.
Results
The analysis included 36 patients. After median follow-up of 48 months, median overall survival (OS) was 58.5 months. Three- and 5-year OS was 55.4 and 46.2%, respectively. Patients who underwent complete macroscopic CRS had significantly better survival than those treated with incomplete CRS, with median OS not achieved and of 20.1 months, respectively 95% confidence interval (CI) 4.4–30.5,
p
< 0.001. There were no postoperative deaths, and 37.9% of patients had major complications.
Conclusion
CRS and HIPEC may increase long-term survival in selected patients with peritoneal metastases of urachus origin, especially when complete CRS is achieved.
The Las Vegas Wash (LW) delivers tertiary-treated municipal wastewater effluent, nonpotable shallow groundwater seepage, and runoff from the urbanized Las Vegas Valley to Las Vegas Bay (LX) of Lake ...Mead. To investigate the potential for contaminants in LW influent to produce effects indicative of endocrine disruption in vivo, adult male and female common carp (Cyprinus carpio) were exposed in cages for 42-48 d at four sites in Lake Mead: LW, LX, and two reference locations in the lake. End points examined included gonadosomatic index; gonad histology; concentrations of plasma vitellogenin (VTG) and plasma sex steroids (17beta-estradiol (E2), testosterone (T), 11-ketotestosterone (11-KT)); plasma estrogen:androgen ratios (E2:T, E2:11-KT), in vitro production of T by gonad tissue, and hepatopancreas ethoxyresorufin O-deethylase activity. Few differences among fish caged at different sites were potentially attributable to exposure to contaminants
Background: Several chemicals in the environment have the potential to inhibit aromatase, an enzyme critical to estrogen synthesis. Objectives: The objective of this study was to provide a detailed ...characterization of molecular and biochemical responses of female fathead minnows to a model aromatase inhibitor, fadrozole (FAD). Methods: Fish were exposed via water to 0, 3, or 30 μg FAD/L for 8 days and then held in clean water for 8 days, with samples collected at four time points during each 8-day period. We quantified ex vivo steroid production, plasma steroids, and plasma vitellogenin (Vtg) concentrations and analyzed relative transcript abundance of 10 key regulatory genes in ovaries and 3 in pituitary tissue by real-time polymerase chain reaction. Results: Ex vivo 17β-estradiol (E₂) production and plasma E₂ and Vtg concentrations were significantly reduced after a single day of exposure to 3 μg or 30 μg FAD/L. However, plasma E₂ concentrations recovered by the eighth day of exposure in the 3-μg/L group and within 1 day of cessation of exposure in the 30-μg/L group, indicating concentration- and time-dependent physiologic compensation and recovery. Concentration-dependent increases in transcripts coding for aromatase (A isoform), cytochrome P450 side-chain cleavage, steroidogenic acute regulatory protein, and follicle-stimulating hormone receptor all coincided with increased E₂ production and recovery of plasma E₂ concentrations. Conclusions: Results of this research highlight the need to consider compensation/adaptation and recovery when developing and interpreting short-term bioassays or biomarkers or when trying to predict the effects of chemical exposures based on mode of action.
The National Status & Trends (NS&T, 1986–1993) and the International Mussel Watch (IMW, 1991–1992) programmes provide a good coverage of a broad range of environmental conditions along the North, ...Central and South American coasts. Total concentrations of DDTs, chlordane-related compounds, PCBs and PAHs present fairly homogeneous distributions along the northern Gulf of Mexico coast, with very few sites showing extremely high or low concentrations. In contrast, a larger variability in the geographical distribution of some of these organic contaminants was observed for IMW sites. For example, high concentrations of DDT and its metabolites, DDD and DDE, were generally found in tropical and subtropical areas as compared to more temperate zones of South America. ‘Industrial’ contaminants, such as PCBs and PAHs, have similar distributions with the highest concentrations encountered generally along the southern South Atlantic coast. An overall comparison of the concentrations of these organic contaminants measured at NS&T and IMW sites indicates that contamination is significantly higher along the northern coast of the Gulf of Mexico.
Lake Shihwa is an artificial lake, located on the west coast of Korea, that has experienced environmental deterioration since 1994, when it was formed by construction of a sea dike. This study used ...instrumental analysis and in vitro bioassays to characterize organic contaminants in sediment collected from 11 stations on Lake Shihwa. Alkylphenol (AP) concentrations in Lake Shihwa sediment ranged from 20.2 to 1,820 ng/g nonylphenol and from 4.69 to 50.5 ng/g octylphenol, on a dry weight basis. Maximum concentrations of polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides, and polychlorinated biphenyls (PCBs) were 30.8, 2.26, and 12.3 ng/g (dry weight), respectively. Significant estrogenic activity was associated with fractions containing APs. Mass‐balance analysis suggested that reported concentrations of APs account for less than 20% of the estrogenic activity observed. No significant dioxinlike activity was associated with fractions containing classic aryl hydrocarbon receptor agonists, such as PCBs, but the mid‐polarity fractions containing PAHs and most polar fractions yielded significant dioxinlike activity. Overall, most of the in vitro bioassay responses appear to have been caused by unidentified and/or undetectable compounds associated with Lake Shihwa sediment.
Abstract Objective An unclear aspect of digital pleural drainage technology is whether it can benefit all lung resection patients or only those who have a postoperative air leak. The aim of this ...study was to evaluate the impact of digital pleural drainage on time to chest tube removal and length of hospitalization, taking into consideration postoperative air leak status. Methods A single-center, randomized, controlled, open-label, parallel-group trial was conducted. On postoperative day 1, stratification according to air leak status was performed by 2 independent, blinded observers. Patients were randomized to a water-sealed, pleural drainage device (analog) or to a digital device (digital). Results In both air leak groups (no air leak = 87; air leak = 85), patient factors and operative details were comparable. In the no air leak group, the difference in median chest tube drainage between analog and digital randomization arms was not statistically significant (3 days vs 2.9 days; P = .05). Median length of stay was also comparable in that group (analog = 4.3 days; digital = 4 days; P = .09). In patients with an air leak, similar findings were observed for chest tube duration (analog = 5.6 days; digital = 4.9 days; P = .11) and length of stay (analog = 6.2 days; digital = 6.2 days; P = .36). Chest tube clamping trials were significantly reduced in the digital arm of the air leak absent (0% vs 16%; P = .01) and air leak present groups (23% vs 50%; P = .01). Conclusions Although digital devices decreased tube clamping trials, the impact on duration of chest tube drainage and hospital stay was not statistically significant, even after stratifying by postoperative air leak status.
Embryos of the green frog (Rana clamitans) were collected from the field and exposed to 1 of 6 water-borne treatments for 273 d (mid July 2001 to mid April 2002). The treatments were 0, 10, or 25 ...μg/L atrazine, 0.005% ethanol (EtOH), or 0.1 mg/L estradiol or dihydrotestosterone carried in 0.005% EtOH. Treatments were applied in a static renewal system with a 50% test solution replacement approximately every 3 d. Following the exposure period, tadpoles were reared in freshwater until metamorphosis or until study termination (at d 506). Time to initiate and complete metamorphosis, stage-specific mortality, length and weight at metamorphosis, and gross morphology and histology of the gonads were examined. At environmentally relevant concentrations, atrazine did not consistently affect growth or metamorphosis. Compared to controls, the length of the larval period was greater in tadpoles exposed to 10 μg/L atrazine. However, the length of the larval period was not markedly different between tadpoles in the control and 25 μg/L atrazine treatments. Neither gross gonadal morphology nor histopathology of the gonads in postmetamorphic frogs was significantly altered in response to atrazine exposure. This study provides evidence that environmentally relevant concentrations of atrazine do not adversely affect the growth or reproductive development of R. clamitans.
Sediments from inland areas and open bays along the Korean coast were analyzed to examine the distribution of dioxin-like and estrogenic compounds. Concentrations of target chemicals varied ...considerably among locations (Lake Shihwa, Masan Bay, and Kwangyang Bay) and between inland and coastal areas. Principal component analysis (PCA) of contaminants measured in sediments showed that all of the inland locations from Lake Shihwa were highly contaminated, and the variations among locations were explained predominantly by the distribution of alkylphenols and polycyclic aromatic hydrocarbons (PAHs). PCA of PAH congener profiles among locations indicated that automobiles were a major source of PAH contamination. Dioxin-like and estrogenic activities associated with sediment from inland sites were approximately three- and six-fold, respectively, greater than those associated with open bay locations. The target dioxin-like and estrogenic compounds measured in raw extracts of sediments accounted for approximately 20% and 40% of the activities measured in the sediment extracts. The results suggest that a combination of instrumental and bioanalytical measurements of dioxin-like and estrogenic compounds is a valuable approach to screen, identify, and prioritize the risks posed by contaminants in complex environmental matrices.
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