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Selected AbstractsEffects of stream restoration and wastewater treatment plant effluent on fish communities in urban streamsFRESHWATER BIOLOGY, Issue 10 2006ROBERT M. NORTHINGTON Summary 1. Fish community characteristics, resource availability and resource use were assessed in three headwater urban streams in Piedmont North Carolina, U.S.A. Three site types were examined on each stream; two urban (restored and unrestored) and a forested site downstream of urbanisation, which was impacted by effluent from a wastewater treatment plant (WWTP). Stream basal resources, aquatic macroinvertebrates, terrestrial macroinvertebrates and fish were collected at each site. 2. The WWTPs affected isotope signatures in the biota. Basal resource, aquatic macroinvertebrate and fish ,15N showed significant enrichments in the downstream sites, although ,13C signatures were not greatly influenced by the WWTP. Fish were clearly deriving a significant part of their nutrition from sewage effluent-derived sources. There was a trend towards lower richness and abundance of fish at sewage-influenced sites compared with urban restored sites, although the difference was not significant. 3. Restored stream sites had significantly higher fish richness and a trend towards greater abundance compared with unrestored sites. Although significant differences did not exist between urban restored and unrestored areas for aquatic and terrestrial macroinvertebrate abundances and biotic indices of stream health, there appeared to be a trend towards improvements in restored sites for these parameters. Additional surveys of these sites on a regular basis, along with maintenance of restored features are vital to understanding and maximising restoration effectiveness. 4. A pattern of enriched ,13C in fish in restored and unrestored streams in conjunction with enriched ,13C of terrestrial invertebrates at these sites suggests that these terrestrial subsidies are important to the fish, a conclusion also supported by isotope cross plots. Furthermore, enriched ,13C observed for terrestrial invertebrates is consistent with some utilisation of the invasive C4 plants that occur in the urban riparian areas. [source] Protein kinase C involvement in aloe-emodin- and emodin-induced apoptosis in lung carcinoma cellBRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2001Hong-Zin Lee This study demonstrated aloe-emodin- and emodin-induced apoptosis in lung carcinoma cell lines CH27 (human lung squamous carcinoma cell) and H460 (human lung non-small cell carcinoma cell). Aloe-emodin- and emodin-induced apoptosis was characterized by nuclear morphological changes and DNA fragmentation. During apoptosis, an increase in cytochrome c of cytosolic fraction and activation of caspase-3, identified by the cleavage of its proform, were observed. To elucidate whether the expression of protein kinase C (PKC) isozymes are involved in aloe-emodin- and emodin-induced apoptosis, this study examined the changes of PKC isozymes by Western blotting techniques during aloe-emodin- and emodin-induced apoptosis. The expression of PKC isozymes involved in aloe-emodin- and emodin-induced apoptosis of CH27 and H460 cells. In this study, aloe-emodin and emodin induced the changes of each of PKC isozymes in CH27 and H460 cells. The decrease in the expression of PKC, and , may play a critical role in aloe-emodin- and emodin-induced apoptosis in CH27 and H460 cells. The present study also demonstrated that PKC stimulation occurs at a site downstream of caspase-3 in the emodin-mediated apoptotic pathway. British Journal of Pharmacology (2001) 134, 1093,1103; doi:10.1038/sj.bjp.0704342 [source] Antidepressants and their metabolites in municipal wastewater, and downstream exposure in an urban watershedENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2010Chris D. Metcalfe Abstract Antidepressants are a widely prescribed group of pharmaceuticals that can be biotransformed in humans to biologically active metabolites. In the present study, the distribution of six antidepressants (venlafaxine, bupropion, fluoxetine, sertraline, citalopram, and paroxetine) and five of their metabolites was determined in a municipal wastewater treatment plant (WWTP) and at sites downstream of two WWTPs in the Grand River watershed in southern Ontario, Canada. Fathead minnows (Pimephales promelas) caged in the Grand River downstream of a WWTP were also evaluated for accumulated antidepressants. Finally, drinking water was analyzed from a treatment plant that takes its water from the Grand River 17 km downstream of a WWTP. In municipal wastewater, the antidepressant compounds present in the highest concentrations (i.e., >0.5 µg/L) were venlafaxine and its two demethylation products, O - and N -desmethyl venlafaxine. Removal rates of the target analytes in a WWTP were approximately 40%. These compounds persisted in river water samples collected at sites up to several kilometers downstream of discharges from WWTPs. Venlafaxine, citalopram, and sertraline, and demethylated metabolites were detected in fathead minnows caged 10 m below the discharge from a WWTP, but concentrations were all <7 µg/kg wet weight. Venlafaxine and bupropion were detected at very low (<0.005 µg/L) concentrations in untreated drinking water, but these compounds were not detected in treated drinking water. The present study illustrates that data are needed on the distribution in the aquatic environment of both the parent compound and the biologically active metabolites of pharmaceuticals. Environ. Toxicol. Chem. 2010;29:79,89. © 2009 SETAC [source] Reproductive health of bass in the Potomac, USA, drainage: Part 2.ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 5 2009Seasonal occurrence of persistent, emerging organic contaminants Abstract The seasonal occurrence of organic contaminants, many of which are potential endocrine disruptors, entering the Potomac River, USA, watershed was investigated using a two-pronged approach during the fall of 2005 and spring of 2006. Passive samplers (semipermeable membrane device and polar organic chemical integrative sampler [POCIS]) were deployed in tandem at sites above and below wastewater treatment plant discharges within the watershed. Analysis of the samplers resulted in detection of 84 of 138 targeted chemicals. The agricultural pesticides atrazine and metolachlor had the greatest seasonal changes in water concentrations, with a 3.1- to 91-fold increase in the spring compared with the level in the previous fall. Coinciding with the elevated concentrations of atrazine in the spring were increasing concentrations of the atrazine degradation products desethylatrazine and desisopropylatrazine in the fall following spring and summer application of the parent compound. Other targeted chemicals (organochlorine pesticides, polycyclic aromatic hydrocarbons, and organic wastewater chemicals) did not indicate seasonal changes in occurrence or concentration; however, the overall concentrations and number of chemicals present were greater at the sites downstream of wastewater treatment plant discharges. Several fragrances and flame retardants were identified in these downstream sites, which are characteristic of wastewater effluent and human activities. The bioluminescent yeast estrogen screen in vitro assay of the POCIS extracts indicated the presence of chemicals that were capable of producing an estrogenic response at all sampling sites. [source] Seasonality effects on pharmaceuticals and s -triazine herbicides in wastewater effluent and surface water from the Canadian side of the upper Detroit RiverENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 9 2006Wen Yi Hua Abstract The influence of seasonal changes in water conditions and parameters on several major pharmacologically active compounds (PhACs) and s -triazine herbicides was assessed in the wastewater and sewage treatment plant (WSTP) effluent as well as the downstream surface water from sites on the Canadian side of the upper Detroit River, between the Little River WSTP and near the water intake of a major drinking water treatment facility for the City of Windsor (ON, Canada). The assessed PhACs were of neutral (carbamazepine, cotinine, caffeine, cyclophosphamide, fluoxetine, norfluoxetine, pentoxifylline, and trimethoprim) and acidic (ibuprofen, bezafibrate, clofibric acid, diclofenac, fenoprofen, gemfibrozil, indomethacin, naproxen, and ketoprofen) varieties. The major assessed s -triazine herbicides were atrazine, simazine, propazine, prometon, ametryn, prometryn, and terbutryn. At sampling times from September 2002 to June 2003, 15 PhACs were detected in the WSTP effluent at concentrations ranging from 1.7 to 1,244 ng/L. The PhAC concentrations decreased by as much 92 to 100% at the Little River/Detroit River confluence because of the river dilution effect, with further continual decreases at sites downstream from the WSTP. The only quantifiable s -triazine in WSTP effluent, atrazine, ranged from 6.7 to 200 ng/L and was higher in Detroit River surface waters than in WSTP effluent. Only carbamazepine, cotinine, and atrazine were detectable at the low-nanogram and subnanogram levels in surface waters near a drinking water intake site. Unlike the PhACs, atrazine in the Detroit River is not attributable to point sources, and it is heavily influenced by seasonal agricultural usage and runoff. Detroit River surface water concentrations of carbamazepine, cotinine, and atrazine may present a health concern to aquatic wildlife and to humans via the consumption of drinking water. [source] Phorbol esters and adenosine affect the readily releasable neurotransmitter pool by different mechanisms at amphibian motor nerve endingsTHE JOURNAL OF PHYSIOLOGY, Issue 2 2003T. J. Searl Phorbol esters and adenosine have been proposed to interact at common sites downstream of calcium entry at amphibian motor nerve endings. We thus studied the actions and interactions of phorbol esters and adenosine using electrophysiological recording techniques in conjunction with both binomial statistical analysis and high-frequency stimulation at the amphibian neuromuscular junction. To begin this study, we confirmed previous observations that synchronous evoked acetylcholine (ACh) release (reflected as endplate potentials, EPPs) is well described by a simple binomial distribution. We then used binomial analysis to study the effects of the phorbol ester phorbol dibutyrate (PDBu, 100 nm) and adenosine (50 µm) on the binomial parameters n (the number of calcium charged ACh quanta available for release) and p (the average probability of release), where the mean level of evoked ACh release (m) =np. We found that PDBu increased m by increasing the parameter n whilst adenosine reduced m by reducing n; neither agent affected the parameter p. PDBu had no effect on either the potency or efficacy of the inhibition produced by adenosine. Subtle differences between these two agents were revealed by the patterns of EPPs evoked by high-frequency trains of stimuli. Phorbol esters increased ACh release during the early phase of stimulation but not during the subsequent plateau phase. The inhibitory effect of adenosine was maximal at the beginning of the train and was still present with reduced efficacy during the plateau phase. When taken together with previous findings, these present results suggest that phorbol esters increase the immediately available store of synaptic vesicles by increasing the number of primed vesicles whilst adenosine acts at a later stage of the secretory process to decrease the number of calcium-charged primed vesicles. [source] A phase I/II study of weekly high-dose erlotinib in previously treated patients with nonsmall cell lung cancer,CANCER, Issue 5 2006Daniel T. Milton MD Abstract BACKGROUND. Preclinical studies have suggested that erlotinib at high doses may inhibit additional sites downstream of the epidermal growth factor receptor (EGFR), resulting in greater antitumor efficacy. The objective of this study was to determine the tolerability and efficacy of high-dose erlotinib administered on a weekly schedule to patients with advanced nonsmall cell lung cancer (NSCLC). METHODS. The authors conducted a Phase I/II trial of weekly erlotinib in patients with progressive NSCLC who had received previous chemotherapy. In the Phase I portion, patients were enrolled in 3-patient cohorts at erlotinib dose levels of 1200 mg, 1600 mg, and 2000 mg once weekly. The Phase II portion was designed to determine the major objective response rate of the dose identified in the Phase I portion of the trial. RESULTS. Twenty-seven patients were enrolled. No dose-limiting toxicity was observed. Grade 1 and 2 rash and diarrhea were the principle toxicities, and each occurred in 92% of patients. Among 21 patients who were treated at the Phase II dose of 2000 mg weekly, a single objective response was identified, yielding a response rate of 5% (95% confidence interval, 0.2,22%). For this cohort, the median survival was 9.5 months. The sole radiographic response occurred in a patient whose pretreatment tumor specimen harbored an EGFR exon 19 deletion. CONCLUSIONS. Erlotinib at a dose of 2000 mg administered weekly was tolerated well by these patients with advanced NSCLC. The 5% objective response rate did not reach the stated objective at the interim efficacy analysis, prompting the closure of the study. Cancer 2006. © 2006 American Cancer Society. [source] | |||||||||||||