Field-scale monitoring of pharmaceutical compounds applied to active golf courses by recycled water.

The scarcity of potable water in arid and semiarid environments has led to the wider use of recycled water for irrigating agricultural fields, parks, golf courses, and other areas. One concern using recycled water as a source of irrigation has been the presence, fate, and transport of pharmaceutical compounds in water that percolates below the root zone of plants; however, very few multiyear field studies have been reported in the peer-reviewed literature. Here, we assessed compound mass flux of 13 pharmaceuticals in the fairways of four golf courses in the southwestern United States during a 2-yr field study. The sites varied by climate and soil type but were similar regarding turfgrass management. The results showed the presence of at least one pharmaceutical compound in nearly all samples collected, although concentrations were substantially lower after transport through the soil. Percent reduction in compound mass fluxes in drainage water was effectively 100% in 22 of 52 cases, 98 to 100% in 27 of 52 cases, and 73 to 94% in 3 of 52 cases (a case is defined as a specific compound measured at a specific site). Mass fluxes migrating below the root zone were calculated as <250 × 10 g ha for all compounds and >100 × 10 g ha in only two cases. For cases where the majority of the analyses were reportable, all fluxes were <8.80 × 10 g ha. Carbamazepine, meprobamate, and sulfamethoxazole were most commonly found in drainage water, representing nearly 80% of all reportable detections. This research demonstrates the potential of turfgrass/soil systems to reduce contaminant loading below the root zone and potentially toward groundwater.

Association between water consumption from polycarbonate containers and bisphenol A intake during harsh environmental conditions in summer.

With the exception of polycarbonate (PC) baby bottles, little attention has been paid to bisphenol A (BPA) intake from packaged water consumption (PC water dispensers), especially during summer weather conditions. We determined the magnitude and variability of urinary BPA concentrations during summer in 35 healthy individuals largely relying upon PC packaged water to satisfy their potable needs. We used liquid chromatography-tandem mass spectrometry to measure urinary BPA concentrations. A questionnaire was administered in July/August and a spot urine sample was collected on the same day and 7 days after the completion of the interview (without intervention). Linear regression was performed to assess the association of variables, such as water consumption from different sources, on urinary BPA levels for the average of the two urine samples. A significant positive association (p = 0.017) was observed between PC water consumption and urinary BPA levels in females, even after adjusting for covariates in a multivariate regression model. The geometric mean of daily BPA intake back-calculated from urinary BPA data was 118 ng · (kg bw)(-1) · day(-1), nearly double the average intake levels observed in biomonitoring studies worldwide. High urinary BPA levels were partially ascribed to summer's high PC water consumption and weather characteristics (high temperatures, >40 °C; very high UV index values, >8), which could be causing BPA leaching from PC. It is suggested that PC-based water consumption could serve as a proxy for urinary BPA, although the magnitude of its relative contribution to overall daily intake requires further investigation.

Designing monitoring programs for chemicals of emerging concern in potable reuse--what to include and what not to include?

This study discussed a proposed process to prioritize chemicals for reclaimed water monitoring programs, selection of analytical methods required for their quantification, toxicological relevance of chemicals of emerging concern regarding human health, and related issues. Given that thousands of chemicals are potentially present in reclaimed water and that information about those chemicals is rapidly evolving, a transparent, science-based framework was developed to guide prioritization of which compounds of emerging concern (CECs) should be included in reclaimed water monitoring programs. The recommended framework includes four steps: (1) compile environmental concentrations (e.g., measured environmental concentration or MEC) of CECs in the source water for reuse projects; (2) develop a monitoring trigger level (MTL) for each of these compounds (or groups thereof) based on toxicological relevance; (3) compare the environmental concentration (e.g., MEC) to the MTL; CECs with a MEC/MTL ratio greater than 1 should be prioritized for monitoring, compounds with a ratio less than '1' should only be considered if they represent viable treatment process performance indicators; and (4) screen the priority list to ensure that a commercially available robust analytical method is available for that compound.

Carbonic anhydrase IX is a predictive marker of doxorubicin resistance in early-stage breast cancer independent of HER2 and TOP2A amplification.

BACKGROUND: In early-stage breast cancer, adjuvant chemotherapy is associated with significant systemic toxicity with only a modest survival benefit. Therefore, there is considerable interest in identifying predictive markers of response to therapy. Doxorubicin, one of the most common drugs used to treat breast cancer, is an anthracycline chemotherapeutic agent, a class of drugs known to be affected by hypoxia. Accordingly, we examined whether expression of the endogenous hypoxia marker carbonic anhydrase IX (CA IX) is predictive of outcome in early-stage breast cancer patients treated with doxorubicin. METHODS: We obtained 209 early-stage pre-treatment surgically-resected breast tumours from patients, who received doxorubicin in their chemotherapeutic regimen and had >10 years of follow-up. Immunohistochemistry was used to detect CA IX, and we used fluorescence in situ hybridisation to detect both human epidermal growth factor receptor (HER2) and DNA topoisomerase II-alpha (TOP2A) gene amplification. RESULTS: Carbonic anhydrase IX intensity was significantly correlated with progression-free survival (PFS) and overall survival (OS) in patients receiving 300 mg m(-2) of doxorubicin (HR=1.82 and 3.77; P=0.0014 and 0.010, respectively). There was a significant, inverse correlation between CA IX score and oestrogen receptor expression, but no significant correlations were seen with either HER2 or TOP2A ratio. CONCLUSION: We demonstrate that CA IX expression is correlated with worse PFS and OS for breast cancer patients treated with doxorubicin, independent of HER2 or TOP2A gene amplification. This study provides evidence that using CA IX to detect hypoxia in surgically-resected breast tumours may be of clinical use in choosing an appropriate chemotherapy regimen.

Establishment and characterization of a canine soft tissue sarcoma cell line.

Stringently controlled in vitro experiments are a necessary part of translational research. Cell lines are useful for exploring the underlying biology of cancer. Very few canine soft tissue sarcoma cell lines exist. This report describes the establishment of a new canine soft tissue sarcoma cell line (MBSa1) derived from a high-grade, metastatic neurofibrosarcoma. The primary tumor tissue was obtained from a 12-year-old neutered male German Shepherd Dog and was maintained in tissue culture for a minimum of 20 passages over 7 months. MBSa1 was injected into athymic mice to determine tumorigenicity. Five million cells were injected into the subcutis of the right flank of athymic nude mice. Nine of the 10 mice grew tumors 1 cm or larger within 8 weeks of cell injection. The large number of in vitro passages coupled with solid tumor formation in athymic nude mice demonstrates that MBSa1 has been immortalized and is tumorigenic.

Association of MRI T1 relaxation time with neuropsychological test performance in manganese- exposed welders.

This study examines the results of neuropsychological testing of 26 active welders and 17 similar controls and their relationship to welders' shortened MRI T1 relaxation time, indicative of increased brain manganese (Mn) accumulation. Welders were exposed to Mn for an average duration of 12.25 years to average levels of Mn in air of 0.11±0.05mg/m3. Welders scored significantly worse than controls on Fruit Naming and the Parallel Lines test of graphomotor tremor. Welders had shorter MRI T1 relaxation times than controls in the globus pallidus, substantia nigra, caudate nucleus, and the anterior prefrontal lobe. 63% of the variation in MRI T1 relaxation times was accounted for by exposure group. In welders, lower relaxation times in the caudate nucleus and substantia nigra were associated with lower neuropsychological test performance on tests of verbal fluency (Fruit Naming), verbal learning, memory, and perseveration (WHO-UCLA AVLT). Results indicate that verbal function may be one of the first cognitive domains affected by brain Mn deposition in welders as reflected by MRI T1 relaxation times.

Simultaneous administration of glucose and hyperoxic gas achieves greater improvement in tumor oxygenation than hyperoxic gas alone.

PURPOSE: To test the feasibility of hyperglycemic reduction of oxygen consumption combined with oxygen breathing (O(2)), to improve tumor oxygenation. METHODS AND MATERIALS: Fischer-344 rats bearing 1 cm R3230Ac flank tumors were anesthetized with Nembutal. Mean arterial pressure, heart rate, tumor blood flow ([TBF], laser Doppler flowmetry), pH, and pO(2) were measured before, during, and after glucose (1 or 4 g/kg) and/or O(2). RESULTS: Mean arterial pressure and heart rate were unaffected by treatment. Glucose at 1 g/kg yielded maximum blood glucose of 400 mg/dL, no change in TBF, reduced tumor pH (0.17 unit), and 3 mm Hg pO(2) rise. Glucose at 4 g/kg yielded maximum blood glucose of 900 mg/dL, pH drop of 0.6 unit, no pO(2) change, and reduced TBF (31%). Oxygen tension increased by 5 mm Hg with O(2). Glucose (1 g/Kg) + O(2) yielded the largest change in pO(2) (27 mm Hg); this is highly significant relative to baseline or either treatment alone. The effect was positively correlated with baseline pO(2), but 6 of 7 experiments with baseline pO(2) < 10 mm Hg rose above 10 mm Hg after combined treatment. CONCLUSION: We demonstrated the feasibility of combining hyperglycemia with O(2) to improve tumor oxygenation. However, some cell lines are not susceptible to the Crabtree effect, and the magnitude is dependent on baseline pO(2). Additional or alternative manipulations may be necessary to achieve more uniform improvement in pO(2).

Stroma-free human hemoglobin A decreases R3230Ac rat mammary adenocarcinoma blood flow and oxygen partial pressure.

We examined the effect of a nitric oxide (NO) quencher, stroma-free human hemoglobin A (HbA0; 0.01, 0.05, 0.1, 0.2 g/kg), on the blood flow measured using the Doppler flow technique, tumor oxygen pressure (pO2) and the diameter of the arterioles using R3230Ac mammary adenocarcinoma as the tumor model. In female Fischer 344 rats with 1-cm-diameter tumors implanted in the lateral aspect of the left quadriceps, intravenous infusion of 0.1 and 0.2 g/kg HbA0 decreased both central tumor and peripheral tumor blood flow by 20-30% (P < 0.05). Tumor pO2 decreased 28% with 0.2 g/kg HbA0, from 15 mm Hg (baseline) to 11 mm Hg at 10 min (P = 0.02). Although 0.2 g/kg HbA0 increased blood flow 55% in the left quadriceps muscle proximal to the implanted tumor (P < 0.05), HbA0 had little effect on blood flow in right quadriceps muscle with no tumor implanted, and increased right quadriceps pO2, from 21 mm Hg (baseline) to 23 mm Hg at 10 min (P = 0.03). HbA0 increased mean arterial pressure 5-10% in a manner that was dependent on dose while heart rate concurrently decreased 9-19%. The diameter of the arterioles supplying the tumor was rapidly reduced 10% by 0.2 g/kg HbA0 (P = 0.037) and remained stable through 60 min of observation (P = 0.005). HbA0 selectively reduces tumor blood flow and tumor pO2 through vasoconstriction of the arterioles supplying the tumor. Vascular NO quenching provides an alternative to NO synthase inhibition as a means to achieve the goal of selective tumor hypoxia.

Preclinical cardiac dysfunction in transfusion-dependent children and young adults detected with low-dose dobutamine stress echocardiography.

Transfusion-dependent (TD) patients develop cardiac iron overload that will eventually lead to cardiac pump failure. Low-dose dobutamine stress echocardiography may complement resting echocardiography and identify preclinical myocardial dysfunction caused by early cardiac hemosiderosis. Twenty-six iron-overloaded TD patients had stress echocardiography with 5 microg/kg per minute of dobutamine. Indexed left ventricular (LV) mass, LV dimensions, meridional wall stress, and cardiac index were significantly increased. TD patients had similar LV shortening fraction by M-mode (40.5% +/- 5.6% vs 39.4% +/- 4.5%) but had a lower mean LV ejection fraction (53.3% +/- 3.9% vs 46.8% +/- 6.9%, P < .002) and a subnormal increase in cardiac index during dobutamine stress (35% +/- 20% vs 11% +/- 16%, P < .0001). Impairment in LV relaxation was demonstrated by a prolonged isovolumetric relaxation time (0.060 +/- 0.005 vs 0.088 +/- 0.019 seconds, P < .0001), increased peak mitral E wave, and abnormal E/A ratio. Asymptomatic TD patients demonstrate decreased systolic functional reserve and abnormal left ventricular relaxation that may be caused by cardiac hemosiderosis. Low-dose dobutamine stress echocardiography may be useful for detecting and following cardiac dysfunction in patients at risk for cardiac hemosiderosis.

Bioconcentration of nonylphenol in fathead minnows (Pimephales promelas).

Bioconcentration of p-nonylphenol (NP) by fathead minnows was determined under laboratory conditions. Fish were exposed continuously for 42 days to 0.33, 0.93 and 2.36 microg NP/l in a flow-through system. NP was Soxhlet extracted from whole fish homogenates with dichloromethane (DCM). The resulting extract was concentrated and bulk lipids removed by gel permeation and silica-gel chromatography. Compounds were identified and quantified by reverse-phase high-pressure liquid chromatography (RP-HPLC) with fluorescence detection. Mass spectrometry was used for verification of peak assignments. Bioconcentration factors (BCFs) ranged from 245 to 380.

Identification and quantitation method for nonylphenol and lower oligomer nonylphenol ethoxylates in fish tissues.

Substantial research is currently focused on the toxicological effects of alkylphenol ethoxylates (APEs) and alkylphenols (APs) on aquatic animals. Considerable data are available on the concentrations of APEs and APs in river systems in the United States; however, few if any data are available on the tissue concentrations of fish living in these rivers. A reliable method for the analysis of nonylphenol (NP) and lower oligomer nonylphenol ethoxylates (NPE1-3) in fish tissues has been developed. Nonylphenol and NPE1-3 were extracted from fish tissues using extractive steam distillation. Normal phase high-performance liquid chromatography (HLPC) was used as a cleanup step prior to analysis by gas chromatography with mass selective detection (GC/MSD) using selected ion monitoring. Optimization of this technique resulted in consistent recoveries in excess of 70%, with the exception of NPE3 (17%). Method detection limits (MDLs) and limits of quantitation using the technique range from 3 to 20 and 5 to 29 ng/g wet weight, respectively. Nonylphenol and NPE1 were detected in subsamples (n = 6) of a single common carp captured in the Las Vegas Bay of Lake Mead (NV, USA) at average concentrations of 184+/-4 ng/g and 242+/-9 wet weight, respectively. Nonylphenol ethoxylates were not detected in the carp collected at Lake Mead.

Effects of nonylphenol ethoxylate exposure on reproductive output and bioindicators of environmental estrogen exposure in fathead minnows Pimephales promelas.

Nonylphenol ethoxylates (NPEOs) were evaluated in the laboratory for potential effects on the reproductive physiology and fecundity of fathead minnows (Pimephales promelas). Groups of three adult male and three female fathead minnows were exposed in a continuous flow-through system to 0, 0.21, 0.65, 2.1, or 7.9 microg NPEO/L for 42 d. Rabbit anti-goldfish vitellogenin (VTG) antiserum was prepared and a competitive enzyme-linked immunosorbent assay (ELISA) was adapted for measurement of plasma VTG in fish following exposure. Plasma 17beta-estradiol (E2) and testosterone (T) were also quantified by ELISA at the end of the exposure. Neither survival nor fecundity of fathead minnows exhibited a concentration-dependent response to NPEOs. No significant differences were observed in plasma VTG concentrations among treatments for males or females. Mean plasma VTG concentrations in females ranged from 291.7 to 895.1 microg VTG/ml among treatments and did not overlap with mean concentrations measured in the plasma of males, which ranged from less than the method detection limit (0.27 microg VTG/ml) to 3.2 microg VTG/ml. Plasma E2 concentrations exhibited a significant difference between males and females within all NPEO treatments, but no differences were observed among treatments. Similarly, plasma T concentrations did not exhibit a concentration-dependent response to NPEOs.

A transducer to measure isometric elbow moments.

OBJECTIVE: The purpose of this study was to design and implement a transducer to measure accurately the isometric elbow moments produced by individuals with tetraplegia. DESIGN: The device needed to be insensitive to off-axis moments and proximal joint motions and be capable of being used over a wide range of elbow and shoulder positions in an outpatient clinic setting. BACKGROUND: Measurement of the smaller isometric moments produced by individuals with tetraplegia is especially sensitive to the errors that can be introduced by inaccurate lever arm determination, off-axis loads, and proximal joint motions. Devices traditionally utilized for quantifying isometric strength are difficult to implement for the spinal cord injured population. METHODS: The elbow moment transducer consists of two four-bar parallelogram linkages joined by a lockable pivot. Strain gauges mounted on one beam of the parallelogram produce an output proportional to the elbow moment. RESULTS: Calibration of the device indicates that it accurately quantifies isometric elbow moments over a range that is appropriate for evaluating elbow extension strength in individuals with tetraplegia. CONCLUSIONS: A device was developed and implemented that accurately quantifies isometric elbow moments over a range that is appropriate for evaluating elbow extension strength in individuals with tetraplegia. RELEVANCE: The ability to quantitatively evaluate elbow strength in persons with tetraplegia is useful for understanding and improving the clinical outcomes of rehabilitative interventions that involve the elbow.

Maternal perceptions of lead poisoning in children with normal and elevated lead levels.

INTRODUCTION: The purpose of this study was to examine mothers' perceptions of the severity and susceptibility of their children to lead poisoning and to determine if a correlation existed between mothers' knowledge of lead poisoning and their children's blood lead levels. It was thought that mothers of children with lead poisoning (lead levels > or = 10 micrograms/dL) would score lower on a test of their perceptions and knowledge of lead poisoning than would mothers of children with normal lead levels (lead levels < or = 9 micrograms/dL). METHOD: A cross-sectional study comparing scores of a questionnaire completed by mothers whose children had elevated blood lead levels and mothers whose children had normal blood lead levels was conducted. RESULTS: No difference was found in the median test score between the 2 groups. For the correct responses on a question-by-question comparison, significant difference existed between groups; however, the percentage of correct responses was not always greater for the mothers of children with normal blood lead levels. DISCUSSION: Mothers' perceptions and knowledge of lead poisoning were not associated with their children's blood lead levels.

SCRAM: A scoring and ranking system for persistent, bioaccumulative, and toxic substances for the North American Great Lakes. Part IV: Results from representative chemicals, sensitivity analysis, and discriminatory power.

The Chemical Scoring and Ranking Assessment Model (SCRAM) has been described in Parts I-III of this series (Snyder et al.: , 1999a; 1999b; 1999c). SCRAM is a chemical scoring and ranking (CSR) system that scores chemicals on the basis of bioaccumulation potential, environmental persistence, and toxicity. Part IV describes various tests and descriptions of the performance of this system. A group of 21 representative chemicals was chosen and scored to test the system. For those chemicals, the percentages of the scores associated with fate-related properties and associated with data uncertainty were determined. The scoring of four of these chemicals is described in greater detail, and the suitability of the scores is discussed. An analysis of the sensitivity of the system to incomplete data sets is presented. And finally, the discriminatory power of the system is described.

SCRAM: A scoring and ranking system for persistent, bioaccumulative, and toxic substances for the North American Great Lakes. Part II: Bioaccumulation potential and persistence.

Part I (Snyder et al.: , 1999a) of this series introduced SCRAM, a chemical scoring and ranking system for contaminants of the North American Great Lakes. Here, in Part II, scoring of the bioaccumulation potential and persistence of chemicals is discussed, including acceptable types of data, specific scoring instructions, and the basis for criteria and scores for these categories of the system. Difficulties encountered during the process of determining which types of data adequately represent the properties of interest are discussed. Also, justification is given for an emphasis on scoring on the basis of persistence.

SCRAM: A scoring and ranking system for persistent, bioaccumulative, and toxic substances for the North American Great Lakes. Part III: Acute and subchronic or chronic toxicity.

In Part I of this series (Snyder: et al., 1999a), the Chemical Scoring and Ranking Assessment Model (SCRAM) was introduced. This system produces scores for chemicals based on their bioaccumulation potential, environmental persistence, and toxicity. In Part II, scoring of the potential for a chemical to persist in the environment and bioaccumulate was described (Snyder et al., 1999b). In Part III, scoring of chemical toxicity is discussed, including definitions and descriptions of effects that are scored, specific scoring instructions, the basis for the criteria and scores, and specific conditions or concerns regarding the types of data used for scoring. A score for each chemical screened is determined from available test data from acute or subchronic and chronic toxicity tests conducted on aquatic and terrestrial organisms. Subchronic and chronic human health effects, including carcinogenicity, are also considered. Part IV includes an evaluation of the performance of the scoring and ranking system (Snyder: et al., 1999c).

SCRAM: A scoring and ranking system for persistent, bioaccumulative, and toxic substances for the North American Great Lakes. Part I: Structure of the scoring and ranking system.

Hundreds of chemical contaminants have been identified in the Great Lakes System of North America. Depending on the agency or organization, various subset lists of these contaminants have been identified as chemicals of potential concern. However, there is no agreement on the method that should be used to make management decisions. Except for consensus on approximately 40 chemicals that most North American agencies agree can cause deleterious effects if released into the environment, no agreement has been reached regarding the priority that contaminants should receive for further action. That leaves hundreds of chemicals that have been, are being, or potentially could be released into the environment that have not been evaluated yet. A profile for potential chemicals of concern is generally thought to include persistence in the environment, potential to bioaccumulate, and ability to cause toxic effects at environmentally relevant concentrations. Except for the International Joint Commission's definition of persistence (> 8 weeks residence time in air, water, soil or sediment), there is little concurrence about what defines these characteristics. For instance, the State of Michigan currently has no established definitions or profiles of persistent, bioaccumulative, toxic substances. Furthermore, there is no standard process to rank chemicals relative to these characteristics. The Chemical Scoring and Ranking Assessment Model (SCRAM) has been developed to provide a process to rank-order chemicals based on these characteristics. The SCRAM system was developed primarily for use in the Great Lakes region of North America and particularly in Michigan, but it is not site-specific. Use of this system may assist in pollution prevention activities and other future chemical control efforts, allowing attention to be focused first on those chemicals likely to present the greatest hazard.