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Biotransformation plays a crucial role in regulating the bioaccumulation potential and toxicity of organic compounds in organisms but is, in general, poorly understood for emerging contaminants. Here, we have used diclofenac as a model compound to study the impact of biotransformation on the bioaccumulation potential and toxicity in two keystone aquatic invertebrates: Gammarus pulex and Hyalella azteca . In both species, diclofenac was transformed into several oxidation products and conjugates, including two novel products, that is, diclofenac taurine conjugate (DCF-M403) and unexpected diclofenac methyl ester (DCF-M310.03). The ratios of biotransformation products to parent compound were 12-17 for DCF-M403 and 0.01-0.7 for DCF-M310.03 after 24 h exposure. Bioconcentration factors (BCFs) of diclofenac were 0.5 and 3.2 L kg ww -1 in H. azteca and G. pulex , respectively, whereas BCFs of DCF-M310.03 was 164.5 and 104.7 L kg ww -1 , respectively, representing a 25- to 110-fold increase. Acute toxicity of DCF-M310.03 was also higher than the parent compound in both species, which correlated well with the increased bioconcentration potential. The LC 50 of diclofenac in H. azteca was 216 mg L -1 , while that of metabolite DCF-M310.03 was reduced to only 0.53 mg L -1 , representing a 430-fold increase in acute toxicity compared to diclofenac. DCF-M403 is less toxic than its parent compound toward H. azteca , which may be linked to its slightly lower hydrophobicity. Furthermore, the transformation of diclofenac to its methyl ester derivative was explored in crude invertebrate extracts spiked with an S -adenosylmethionine cofactor, revealing possible catalysis by an S -adenosylmethionine-dependent carboxylic acid methyltransferase. Methylation of diclofenac was further detected in fish hepatocytes and human urine, indicating a broader relevance. Therefore, potentially methylated metabolites of polar contaminants should be considered for a comprehensive risk assessment in the future.

A major challenge in ecology is to understand determinants of ecosystem functioning and stability in the face of disturbance. Some important species can strongly shape community structure and ecosystem functioning, but their impacts and interactions on ecosystem-level responses to disturbance are less well known. Shallow ponds provide a model system in which to study the effects of such species because some taxa mitigate transitions between alternative ecosystem states caused by eutrophication. We performed pond experiments to test how two foundation species (a macrophyte and a mussel) affected the biomass of planktonic primary producers and its stability in response to nutrient additions. Individually, each species reduced phytoplankton biomass and tended to increase rates of recovery from disturbance, but together the species reversed these effects, particularly with larger nutrient additions. This reversal was mediated by high cyanobacterial dominance of the community and a resulting loss of trait evenness. Effects of the foundation species on primary producer biomass were associated with effects on other ecosystem properties, including turbidity and dissolved oxygen. Our work highlights the important role of foundation species and their interactive effects in determining responses of ecosystem functioning to disturbance.

The main removal process for polar organic micropollutants during activated sludge treatment is biotransformation, which often leads to the formation of stable transformation products (TPs). Because the analysis of TPs is challenging, the use of pathway prediction systems can help by generating a list of suspected TPs. To complete and refine pathway prediction, comprehensive biotransformation studies for compounds exhibiting pertinent functional groups under environmentally relevant conditions are needed. Because many polar organic micropollutants present in wastewater contain one or several amine functional groups, we systematically explored amine biotransformation by conducting experiments with 19 compounds that contained 25 structurally diverse primary, secondary, and tertiary amine moieties. The identification of 144 TP candidates and the structure elucidation of 101 of these resulted in a comprehensive view on initial amine biotransformation reactions. The reactions with the highest relevance were N-oxidation, N-dealkylation, N-acetylation, and N-succinylation. Whereas many of the observed reactions were similar to those known for the mammalian metabolism of amine-containing xenobiotics, some N-acylation reactions were not previously described. In general, different reactions at the amine functional group occurred in parallel. Finally, recommendations on how these findings can be implemented to improve microbial pathway prediction of amine-containing micropollutants are given.

Human body odor is to a large part determined by secretions of glands in the axillary regions. Two key odoriferous principles, 3-methylhex-2-enoic acid (3MH2; 4/5) and 3-hydroxy-3-methylhexanoic acid (HMHA; 6) have been shown to be released from glutamine conjugates secreted in the axilla by a specific N(alpha)-acyl-glutamine aminoacylase (N-AGA) obtained from axilla isolates of Corynebacteria sp. However, the low number of different odorants reported in humans stands in contrast to the observed high inter-individual variability in body odors. Axilla secretions of individual donors were, therefore, analyzed in detail. The secretions were treated with N-AGA, analyzed by GC/MS, and compared to undigested controls. Over 28 different carboxylic acids were released by this enzyme from odorless axilla secretions (Table 1). Many of these body odorants have not been reported before from a natural source, and they include several aliphatic 3-hydroxy acids with 4-Me branches, 3,4-unsaturated, 4-Et-branched aliphatic acids, and a variety of degradation products of amino acids. The odor threshold of some of the acids was found to be in the range of 1 ng. Most of these compounds were present in all donors tested, but in highly variable relative amounts, and they are, thus, candidate molecules as key components of a 'compound odor' determining the individual types of human body odor.

The authors' objectives were as follows: 1) to characterize for the first time the relationship between whole body O2 delivery (DO2) and O2 consumption (VO2) in adult conscious dogs; and 2) to asses the effects of the inhalational anesthetic, halothane, on that relationship. DO2 was varied over a wide range in chronically instrumented dogs by gradual inflation and deflation of a hydraulic occluder implanted around the thoracic inferior vena cava to alter venous return and cardiac output. VO2 was measured at different values of DO2 in dogs in the fully conscious state and again during halothane anesthesia. A "binning" technique indicated that halothane decreased VO2 (P less than 0.01) at any given value of DO2 over a broad range of VO2. A two-line piecewise linear regression analysis technique indicated that halothane decreased (P less than 0.01) the critical O2 delivery (COD) from 20 +/- 3 to 10 +/- 1 ml.kg-1.min-1 and increased (P less than 0.01) O2 extraction at COD from 31 +/- 3 to 40 +/- 2%. However, the DO2-VO2 plots measured in both conscious and halothane-anesthetized dogs did not exhibit a discrete discontinuity but rather were closely fit (correlation coefficient = 0.98) by an exponential equation of the following form: O2 extraction = B1.(1 - exp (-DO2/B2))/DO2, where B1 is the delivery-independent estimate of VO2 and B2 is the "delivery constant," i.e., the DO2 associated with a VO2 equal to 63% of B1. Halothane decreased B1 (P less than 0.01) from 5.3 +/- 0.1 to 3.9 +/- 0.1 ml.kg-1.min-1 and decreased B2 (P less than 0.01) from 5.6 +/- 0.3 to 3.6 +/- 0.3 ml.kg-1.min-1 compared with that measured in conscious dogs. Thus, compared with the conscious state, halothane anesthesia alters the fundamental relationship between DO2 and VO2 and may have a beneficial effect on tissue oxygenation at low values of DO2.

Clamping and declamping during aortic surgery produce a hemodynamically significant myocardial stress. The cardiovascular (CV) response to this stress may be adversely altered by calcium antagonists and beta-adrenoreceptor blockade employed to control symptomatic coronary artery disease. This study evaluated the effect of verapamil (V), propranolol (P), and their combination (P + V) on the CV response to infrarenal abdominal aortic cross-clamping and declamping in anesthetized dogs. Six dogs received P as a bolus of 0.5 mg/kg 20 min before clamping. Six additional dogs received V as a 300 micrograms/kg bolus followed by a V infusion of 6 micrograms/kg/min for 20 min before clamping. A third group of six dogs received the P bolus followed 20 min later by the V regimen (P + V). In both the V and P + V groups, 6 micrograms/kg/min V was infused throughout the clamping and declamping sequence. A fourth group of six control dogs received no cardioactive drugs during the experiment. Heart rate, mean aortic blood pressure, left ventricular end-diastolic pressures, peak rate of rise of left ventricular pressure, cardiac output, and systemic vascular resistance were measured in all animals before aortic cross-clamping, at 5 and 40 min after clamping, and 5 min after declamping. The results demonstrated additive negative chronotropic and inotropic properties of P + V therapy with a more significantly adverse effect than that of either drug alone. The implications of this study warrant added caution when patients treated with these drugs undergo abdominal aortic surgery.

Practicing anesthesiologists are at high risk of hepatitis B infection, but the risk for anesthesia residents has not been assessed. Anesthesia residents at seven universities were surveyed to study the epidemiology of hepatitis B in these trainees. Hepatitis B virus markers in serum were measured and data from questionnaires were used to determine characteristics of anesthetic practice, effectiveness of strategies for hepatitis B virus infection control, and nonvocational hepatitis B risk factors. Of 267 participants, 12.7% (range of the seven centers, 8.7%-22.7%) had serum markers for hepatitis B virus. The seropositivity (17.8%) in anesthesia residents who had completed more than 12 months of nonanesthesia postgraduate clinical training, or who had practiced medicine in another specialty prior to anesthesia, was greater than in the other trainees (9.4%). Based on their risk and the ineffectiveness of current control measures, anesthesia residents who lack hepatitis B virus immunity should be vaccinated prior to or as early as possible in their training.

Clamping and declamping of the infrarenal abdominal aorta may adversely affect cardiovascular function, particularly in the presence of heart disease. This effect may be further altered by drugs used in the treatment of symptomatic coronary artery disease. The effect of nifedipine on the hemodynamic response to aortic clamping and declamping was determined in 12 dogs anesthetized with 50% nitrous oxide and 0.6% end-tidal isoflurane and monitored with aortic, left ventricular (LV), and thermodilution pulmonary artery catheters. Six dogs received a nifedipine bolus of 100 micrograms/kg followed by an infusion of 4 micrograms/kg/min. Six dogs did not receive any nifedipine and served as controls. Before clamping, nifedipine produced immediate decreases in arterial pressure, systemic vascular resistance (SVR), and LV dP/dt, and a modest increase in cardiac output (CO). During aortic clamping, nifedipine-treated dogs demonstrated marked increases in heart rate (HR), dP/dt, and CO while maintaining a low SVR. There were no significant changes upon declamping. The nifedipine-treated animals maintained a high CO and low SVR. Thus, nifedipine greatly altered the hemodynamic responses to aortic clamping and declamping. Awareness of these alterations is important when caring for patients being treated with nifedipine who are undergoing aortic surgery.