Diffuse and concentrated nitrogen sewage pollution in island environments with differing treatment systems.

Macroalgae is an under-utilised tool as a bioindicator of anthropogenic nitrogen loading to the coastal environment in the UK. This study compared two island systems-Jersey (Channel Islands) and St Mary's (Isles of Scilly) to assess how differing sewerage infrastructure affects nitrogen loading. A total of 831 macroalgae samples of Fucus vesiculosus and Ulva sp. were analysed for nitrogen isotopes (δ15N). Elevated δ15N values were recorded for Jersey (> 9‰) in St Aubin's Bay-caused by the outflow of the Bellozanne Sewerage Treatment Works (STW). δ15N isoplots maps indicate low diffusion of nitrogen out of St Aubin's Bay. St Mary's produced a varied δ15N isoplot map in comparison. δ15N was typically lower and is attributed to a smaller population and inefficient STW. Outflow of sewage/effluent at Morning Point, Hugh Town and Old Town produced elevated δ15N values in comparison to the island average. St Mary's inefficient sewerage treatment and reliance on septic tanks/soakaways complicates δ15N interpretation although it still indicates that nitrogen pollution is an island-wide issue. Future sewerage development and upgrades on islands are required to prevent similar effluent environmental issues as recorded in St Aubin's Bay. This study advocates the use of macroalgae as a bioindicator of nitrogen effluent in the marine environment.

Quantifying the Metabolites of the Methylerythritol 4-Phosphate (MEP) Pathway in Plants and Bacteria by Liquid Chromatography-Triple Quadrupole Mass Spectrometry.

The 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway occurs in the plastids of higher plants and in most economically important prokaryotes where it is responsible for the biosynthesis of the isoprenoid building blocks, isopentenyl diphosphate and dimethylallyl diphosphate. These five-carbon compounds are the substrates for the enormous variety of terpenoid products, including many essential metabolites and substances of commercial value. Increased knowledge of the regulation of the MEP pathway is critical to understanding many aspects of plant and microbial metabolism as well as in developing biotechnological platforms for producing these commercially valuable isoprenoids. To achieve this goal, researchers must have the ability to investigate the in vivo kinetics of the pathway by accurately measuring the concentrations of MEP pathway metabolites. However, the low levels of these metabolites complicate their accurate determination without suitable internal standards. This chapter describes a sensitive method to accurately determine the concentrations of MEP pathway metabolites occurring at trace amounts in biological samples using liquid chromatography coupled to triple quadrupole mass spectrometry. In addition, simple protocols are given for producing stable isotope-labeled internal standards for these analyses.

Myelin-associated glycoprotein binding to gangliosides. Structural specificity and functional implications.

Myelin-associated glycoprotein (MAG), which mediates certain myelin-neuron cell-cell interactions, is a lectin that binds to sialylated glycoconjugates. Gangliosides, the most abundant sialylated glycoconjugates in the brain, may be the functional neuronal ligands for MAG. Cells engineered to express MAG on their surface adhered specifically to gangliosides bearing an alpha 2,3-linked N-acetylneuraminic acid on a terminal galactose, with the following relative potency: GQ1b alpha >> GD1a, GT1b >> GM3, GM4 (GM1, GD1b, GD3, and GQ1b did not support adhesion). MAG binding was abrogated by modification of the carboxylic acid, any hydroxyl, or the N-acetyl group of the ganglioside's N-acetylneuraminic acid moiety. Related immunoglobulin (Ig) superfamily members either failed to bind gangliosides (CD22) or bound with less stringent specificity (sialoadhesin), whereas a modified form of MAG (bearing three of its five extra-cellular Ig-like domains) bound only GQ1b alpha. Enzymatic removal of sialic acids from the surface of intact nerve cells altered their functional interaction with myelin. These data are consistent with a role for gangliosides in MAG-neuron interactions.

Analysis of black tea theaflavins by non-aqueous capillary electrophoresis.

In this study a new capillary electrophoresis (CE) method was developed to quantify the four major theaflavins occurring in black tea. Where aqueous based CE methods showed poor selectivity and considerable band broadening, non-aqueous CE achieved baseline separation of the theaflavins within 10 min. The effects of the organic solvent composition and background electrolyte concentration on the separation selectivity and electrophoretic mobilities were investigated. Our optimized separation solution consisted of acetonitrile-methanol-acetic acid (71:25:4, v/v) and 90 mM ammonium acetate. This method was used to analyze three black tea samples.

Phase I study of pegylated liposomal doxorubicin and the multidrug-resistance modulator, valspodar.

Valspodar, a P-glycoprotein modulator, affects pharmacokinetics of doxorubicin when administered in combination, resulting in doxorubicin dose reduction. In animal models, valspodar has minimal interaction with pegylated liposomal doxorubicin (PEG-LD). To determine any pharmacokinetic interaction in humans, we designed a study to determine maximum tolerated dose, dose-limiting toxicity (DLT), and pharmacokinetics of total doxorubicin, in PEG-LD and valspodar combination therapy in patients with advanced malignancies. Patients received PEG-LD 20-25 mg m(-2) intravenously over 1 h for cycle one. In subsequent 2-week cycles, valspodar was administered as 72 h continuous intravenous infusion with PEG-LD beginning at 8 mg m(-2) and escalated in an accelerated titration design to 25 mg m(-2). Pharmacokinetic data were collected with and without valspodar. A total of 14 patients completed at least two cycles of therapy. No DLTs were observed in six patients treated at the highest level of PEG-LD 25 mg m(-2). The most common toxicities were fatigue, nausea, vomiting, mucositis, palmar plantar erythrodysesthesia, diarrhoea, and ataxia. Partial responses were observed in patients with breast and ovarian carcinoma. The mean (range) total doxorubicin clearance decreased from 27 (10-73) ml h(-1) m(-2) in cycle 1 to 18 (3-37) ml h(-1) m(-2) with the addition of valspodar in cycle 2 (P=0.009). Treatment with PEG-LD 25 mg m(-2) in combination with valspodar results in a moderate prolongation of total doxorubicin clearance and half-life but did not increase the toxicity of this agent.