Synthesis of mono- and diglucosiduronates of metabolites of deoxycorticosterone and corticosterone and analysis by a new mass spectrometric technique

By condensing 3 alpha,21-dihydroxy-5 beta-pregnan-20-one, or its appropriate monoacetate, with methyl 2,3,4-tri-O-acetyl-1-bromo-1-deoxy-alpha-D-glucuronate in the Koenigs-Knorr reaction beta-D-glucosiduronates 10, 4, and 7 were obtained as polyacetate methyl esters. Alkaline hydrolysis of these substances cleaved the ester groups and gave the corresponding steroidal glucosiduronic acids 12, 6 and 8. Upon treatment with diazomethane, these acids produced the equivalent methyl esters. The C-3, the C-21 and the C-3,21 glucosiduronates of 3 alpha,21-dihydroxy-5 beta-pregnan-11,20-dione were prepared by previously reported methods and converted into the corresponding C-20 semicarbazones (14, 20 and 26). With C-20 stabilized by the semicarbazone group against reduction, it was possible to reduce the 11-oxo function in these substances to an 11 beta-hydroxyl group; after removal of the semi-carbazone moiety from these products at pH 2.0, glucosiduronic acids 18, 22 and 28 were obtained. The mass spectra of a representative group of the mono- and diglucosiduronic acids and esters were determined by utilizing fast atom bombardment and monitoring ions in both positive and negative modes of operation.     

Factors Controlling the Bioaccessibility of Arsenic(V) and Lead(II) in Soil

The relative oral bioaccessibility of labile Pb(II) and As(V) added to soils was investigated in a well-characterized soil using a physiologically based extraction test (PBET) to simulate metal solubility in a child's digestive system. The effect of soil and PBET (i.e., simulated stomach and small intestine) pH, soil metal concentration, soil to solution ratio, and soil-metal aging time were investigated. Arsenic bioaccessibility was relatively unaffected by a variation in simulated stomach and small intestine pH over the range 2 to 7 and soil pH over the range 4.5 to 9.4. In contrast, Pb(II) bioaccessibility was strongly dependent on both the simulated stomach, small intestine, and soil pH, showing enhanced sequestration and decreased bioaccessibility at higher pH values in all cases. Although the bioaccessibility of Pb(II) was constant over the concentration range of approximately 10 to 10,000?mg/kg, the As(V) bioaccessibility significantly increased over this concentration range. The bioaccessibility of both arsenic and lead increased as the soil-to-solution ratio decreased from 1:40 to 1:100. Additional lead sequestration was not observed during 6 months of soil aging, but As(V) bioaccessibility decreased significantly during this period.     

Location of acyl groups of trehalose-containing lipooligosaccharides of mycobacteria

A variant of a Mycobacterium sp. originating in a patient with Crohn's disease, but not necessarily implicated in the disease, provided a simple version of a newer class of species-specific surface glycolipids, the trehalose-containing lipooligosaccharides. A combination of high-resolution 1H nuclear magnetic resonance, methylation, ethylation, and absolute configurational analysis established the structure of the oligosaccharide unit as beta-D-Glcp(1----3)-alpha-L-Rhap(1----3)-alpha-D-Glcp(1----1)-alph a-D-Glcp (where Glc is glucose, Rha is rhamnose, and p is pyranosyl), and gas chromatography-electron impact mass spectrometry allowed identification of the fatty acyl esters as primarily 2,4-dimethyltetradecanoate. The relative simplicity of the glycolipid combined with the application of a mild methylation procedure and californium-252 plasma desorption mass spectrometry allowed recognition of three such acyl residues on the 3-, 4-, and 6-hydroxyl positions of the terminal glucosyl residue of the trehalose unit. Thus, the glycolipid is decidedly amphipathic yet is clearly not membranous. This observation leads to speculation about the role of these novel lipooligosaccharides in contributing to the outer segment of the hydrophobic barrier of the cell wall of certain mycobacteria.     

Seasonal Mass Migration of Water Boatmen (Hemiptera: Corixidae) as a Wetland–River Linkage and Dietary Subsidy to Riverine Fish

Ecosystems - Cross-boundary movements of organisms can act as important ecosystem linkages by subsidizing food webs. We investigated the magnitude and implications of a little understood food web...     

Dryland Salinity and Ecosystem Distress Syndrome: Human Health Implications

Clearing of native vegetation for agriculture has left 1.047 million hectares of southwest Western Australia affected by dryland salinity, and this area may expand up to a further 1.7–3.4 million hectares if trends continue. Ecosystems in saline-affected regions display many of the classic characteristics of Ecosystem Distress Syndrome, one outcome of which has not yet been investigated in relation to dryland salinity: adverse human health implications. This article seeks to review existing information and identify potential adverse human health effects. Three key potential impacts on human health resulting from dryland salinity are identified: wind-borne dust and respiratory health; altered ecology of the mosquito-borne disease Ross River virus; and mental health consequences of salinity-induced environmental degradation. Given the predicted increase in extent and severity of dryland salinity over coming decades, adverse outcomes of salinity are likely to be further exacerbated, including those related to human health. There is a clear need to investigate the issues discussed in this review and also to identify other potential adverse health effects of dryland salinity. Investigations must be multidisciplinary to sufficiently examine the broad scope of these issues. The relationship between human health and salinity may also be relevant beyond Australia in other countries where secondary soil salinization is occurring.     

Antimicrobial resistance in Escherichia coli isolates from raccoons (Procyon lotor) in Southern Ontario, Canada

We conducted a cross-sectional study to determine the prevalence of antimicrobial resistance (AMR) in fecal Escherichia coli isolates from raccoons (Procyon lotor) living in Ontario, Canada. From June to October 2007, we trapped raccoons in three areas: one primarily urban site around Niagara, one primarily rural site north of Guelph, and one at the Toronto Zoo. In addition, we conducted a longitudinal study at the Toronto Zoo site to investigate the temporal dynamics of fecal E. coli and AMR in raccoons. Reduced susceptibility to ≥1 antimicrobial agent was detected in E. coli isolates from 19% of 16 raccoons at the urban site, 17% of 29 raccoons from the rural site, and 42% of 130 samples collected from 59 raccoons at the zoo site. Raccoons from the zoo site were significantly more likely to shed E. coli with reduced susceptibility to ≥1 antimicrobial agent than animals from the rural site (odds ratio [OR], 3.41; 95% confidence interval [CI], 1.17 to 12.09; P = 0.02). Resistance to expanded-spectrum cephalosporins (and the associated bla(CMY-2) gene) was detected in two animals from the zoo site and one animal from the rural site. Serotyping and pulsed-field gel electrophoresis analysis show that raccoons on the zoo grounds harbor a diverse assemblage of E. coli, with rapid bacterial turnover within individuals over time. Our study indicates that raccoons may shed resistant bacteria of public health significance and that raccoons have the potential to disseminate these bacteria throughout their environment.     

Inhibition of mammalian ribonucleases by endogenous adenosine dinucleotides

The most potent low molecular weight inhibitors of pancreatic RNase superfamily enzymes reported to date are synthetic derivatives of adenosine 5(')-pyrophosphate. Here we have investigated the effects of six natural nucleotides that also incorporate this moiety (NADP(+), NADPH, ATP, Ap(3)A, Ap(4)A, and Ap(5)A) on the activities of RNase A and two of its homologues, eosinophil-derived neurotoxin and angiogenin. With eosinophil-derived neurotoxin and angiogenin, Ap(5)A is comparable to the tightest binding inhibitors identified previously (K(i) values at pH 5.9 are 370 nM and 100 microM, respectively); it ranks among the strongest small antagonists of RNase A as well (K(i)=230 nM). The K(i) for NADPH with angiogenin is similar to that of Ap(5)A. These findings suggest that Ap(5)A and NADPH may serve as useful new leads for inhibitor design. Examination of inhibition under physiological conditions indicates that NADPH, ATP, and Ap(5)A may suppress intracellular RNase activity significantly in vivo.