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Other Endpoints (other + endpoint)
Selected AbstractsEffects of pulp and paper mill effluent on fish: A temporal assessment of fish health across sampling cyclesENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2010Timothy J. Barrett Abstract The Canadian environmental effects monitoring (EEM) program is a regulated, cyclical, industry-funded program designed to determine whether receiving water impacts exist when a mill is in compliance with its discharge limits. The results from three cycles of the fish monitoring program (1992 to 2004) are available from over 200 surveys of fish compared between sites located upstream and downstream of pulp and paper mill effluent outfalls. Previous meta-analyses have shown a national average response pattern across cycles characterized by an increase in endpoints measuring energy storage and growth and a decrease in a reproductive endpoint, consistent with a response of nutrient enrichment in combination with some form of metabolic disruption. Although the national average pattern of effects was temporally consistent, there was some variability in the magnitude of effects among cycles. Questions were raised as to whether the intercycle variability was due to changes in effluent quality or due, at least in part, to other factors. The present study compares responses over the first three cycles, and shows that the choice of sentinel species is likely to be a major contributing factor to the variability in observed effects. Subset analyses using studies from mills that used the same sentinel species across cycles reveal fairly uniform responses and little evidence of significant improvements in overall fish health from cycles one to three. However, a meta-analysis using 1991 data collected from 10 mills before the implementation of the EEM program and data from the same mills collected during cycles one to three of the program reveal significantly reduced effects on relative liver weight and potential improvements in other endpoints. Environ. Toxicol. Chem. 2010;29:440,452. © 2009 SETAC [source] Evaluation of the methoxytriazine herbicide prometon using a short-term fathead minnow reproduction test and a suite of in vitro bioassaysENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2006Daniel L. Villeneuve Abstract Prometon is one of the most consistently detected herbicides in the U.S. environment. However, no previous assessment of the potential for prometon or related methoxytriazine herbicides to act as endocrine-disrupting chemicals has been conducted. This study used an array of in vitro bioassays to assess whether prometon, atraton, terbumeton, or secbumeton might act as potent (ant)agonists of the aryl hydrocarbon, estrogen, androgen, or glucocorticoid receptors or as aromatase inhibitors or inducers in vitro. Potential effects of prometon were also evaluated using a 21-d fathead minnow reproduction assay. Concentrations of methoxytriazines, as great as 1 mg/L (4.4 ,M), did not induce significant dioxin-like responses in H4IIE-luc cells, estrogenic responses in MVLN cells, or androgen or glucocorticoid receptor,mediated responses in MDA-kb2 cells, nor did the methoxytriazines significantly affect aromatase activity in vitro. In the fathead minnow assay, exposure to 20, 200, or 1,000 ,g prometon/L significantly reduced the weight of the male fat pad (an androgen-responsive tissue) relative to body weight. Exposure to 20 ,g prometon/L significantly increased female plasma testosterone concentrations, but the effect was not observed at greater concentrations. Overall, prometon did not significantly reduce fecundity over the 21-d exposure, nor were other endpoints, including plasma vitellogenin and estradiol concentrations, brain and ovary aromatase activity, and male tubercle index, significantly affected. Evidence from our work suggests that prometon may cause subtle endocrine and/or reproductive effects in fathead minnows, but no clear mechanism of action was observed. The relevance of these effects to hazard assessment for the pesticide is uncertain. [source] RDP58 is a novel and potentially effective oral therapy for ulcerative colitisINFLAMMATORY BOWEL DISEASES, Issue 8 2005Simon Travis FRCP Abstract Background: RDP58 is a novel anti-inflammatory d-amino acid decapeptide that inhibits synthesis of proinflammatory cytokines by disrupting cell signaling at the pre-MAPK MyD88-IRAK-TRAF6 protein complex. We therefore evaluated its efficacy and safety in parallel multicenter, double-blind, randomized concept studies in ulcerative colitis (UC). Methods: In the first trial, 34 patients with mild to moderate active UC were randomized (1:2) to placebo (n = 13) or RDP58 100 mg (n = 21). In the second trial, 93 similar patients were randomized (1:1:1) to placebo (n = 30) RDP58 200 mg (n = 31), or RDP 300 mg (n = 32). In both studies, treatment success was defined as a simple clinical colitis activity index score of no more than 3 at 28 days. Sigmoidoscopy and rectal biopsy (at baseline and 28 days) and safety measures (baseline and 28 and 56 days) were other endpoints. Results: Treatment success on RDP 100 mg was 29% versus 46% on placebo (P = 0.46). There were no significant differences in sigmoidoscopy or histology score. In the second study, treatment success on the higher doses of RDP58 (200 and 300 mg) was 71% and 72%, respectively, versus 43% on placebo (P = 0.016). Improvements in sigmoidoscopy scores (41% on 200 mg and 46% on 300 mg versus 32% on placebo) did not reach significance, but histology scores improved significantly (P = 0.002) versus placebo. Overall, adverse events were no different between placebo (3.3 ± 2.4) and RDP58 (2.7 ± 1.4, 300-mg group). Conclusions: RDP58 at a dose of 200 or 300 mg, but not 100 mg, was effective in mild-to-moderate UC. RDP58 was safe and well tolerated, and its novel action makes it an attractive potential therapy. [source] Long-term study of fluticasone propionate aqueous nasal spray in acute and maintenance therapy of nasal polyposisALLERGY, Issue 6 2009R. Jankowski Background:, Topical steroids are first-line medication to control nasal polyposis (NP), a disease with long-term clinical course. Objective:, The aim of this study was to evaluate the efficacy and safety of fluticasone propionate aqueous nasal spray (FPANS) 200 ,g twice a day (bd) after 1 month of treatment, and to compare FPANS 200 ,g bd and FPANS 200 ,g once a day (od) in maintenance and long-term treatment. Methods:, Double-blind, placebo-controlled, 8-month study with three treatment periods (1-month acute period followed with 1-month maintenance period and 6-month follow-up period) was carried out. Group 1 received FPANS 200 ,g bd, during acute, maintenance and follow-up periods, Group 2 received FPANS 200 ,g bd during acute period and FPANS 200 ,g od during maintenance and follow-up periods, and Group 3 received placebo during acute and maintenance periods and FPANS 200 ,g bd during follow-up period. Endpoints were change from baseline in clinic peak nasal inspiratory flow (PNIF), domiciliary evening PNIF, intensity of symptoms and polyposis grade. Results:, After acute period and maintenance periods, FPANS 200 ,g bd was significantly more effective than placebo on all endpoints and more effective than FPANS 200 ,g od after 1-month maintenance period on clinic PNIF, evening PNIF, obstruction, percentage of days with no sense of smell and percentage of nights with no disturbances. The two doses were similar on other endpoints. After the 6-month follow-up period, there was no difference between the two doses of FPANS at all efficacy endpoints. The safety profile of FPANS did not highlight any new or unanticipated adverse events. Conclusion:, The study demonstrated the efficacy of FPANS 200 ,g bd in acute treatment and FPANS 200 ,g od as a sufficient dose to maintain a long-term efficacy in the treatment for NP. [source] Idiopathic thrombocytopenic purpura in childhood: Controversies and solutionsPEDIATRIC BLOOD & CANCER, Issue S5 2006Thomas Kühne MD Abstract Idiopathic thrombocytopenic purpura (ITP) is a bleeding disorder in patients who are otherwise healthy and present with thrombocytopenia with normal red cells and leukocytes. ITP is a diagnosis of exclusion and is in origin heterogeneous. The unknown etiology and the lack of clinical data from controlled prospective studies are reasons for controversies in diagnosis and management. Study endpoints traditionally include the velocity of platelet increase after drug intervention or observation, although a rapid elevation of the platelet count is of questionable clinical value. Evaluation of other endpoints is needed. Pediatr Blood Cancer 2006;47:650,652. © 2006 Wiley-Liss, Inc. [source] | ||||||||||