Anion modulation of taste responses in sodium-sensitive neurons of the hamster chorda tympani nerve

Beidler's work in the 1950s showed that anions can strongly influence gustatory responses to sodium salts. We have demonstrated "anion inhibition" in the hamster by showing that the chorda tympani nerve responds more strongly to NaCl than to Na acetate over a wide range of concentrations. Iontophoretic presentation of Cl- and acetate to the anterior tongue elicited no response in the chorda tympani, suggesting that these anions are not directly stimulatory. Drugs (0.01, 1.0, and 100 microM anthracene-9-carboxylate, diphenylamine-2-carboxylate, 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonate, and furosemide) that interfere with movements of Cl- across epithelial cells were ineffective in altering chorda tympani responses to 0.03 M of either NaCl or Na acetate. Anion inhibition related to movements of anions across epithelial membranes therefore seems unlikely. The chorda tympani contains a population of nerve fibers highly selective for Na+ (N fibers) and another population sensitive to Na+ as well as other salts and acids (H fibers). We found that N fibers respond similarly to NaCl and Na acetate, with spiking activity increasing with increasing stimulus concentration (0.01-1.0 M). H fibers, however, respond more strongly to NaCl than to Na acetate. Furthermore, H fibers increase spiking with increases in NaCl concentration, but generally decrease their responses to increasing concentrations of Na acetate. It appears that anion inhibition applies to taste cells innervated by H fibers but not by N fibers. Taste cells innervated by N fibers use an apical Na+ channel, whereas those innervated by H fibers may use a paracellularly mediated, basolateral site of excitation.     

The Acrylation of Glycerol: A Precursor to Functionalized Lipids

With the objective of expanding the number of functionalized lipids available, the reactive vinyl group of acrylic acid was introduced to triacylglycerol by esterification of glycerol. Didecanoylacryloylglycerol was synthesized from decanoic and acrylic acids and glycerol using K₂O as catalyst. 2 g (21.7 mmol) glycerol, 11.3 g (65.4 mmol) decanoic acid, 6.2 g (86.1 mmol) acrylic acid, 60 ml hexane, and 400 mg K₂O were added to 300-ml closed stainless steel reactor and maintained at 200 °C for 5 h. The resulting product, designated DDA, was isolated at about 40% yield based on the acylglycerol products. The other products included tridecanoylglycerol, diacryloyldecanoylglycerol, and the diacylglycerols of these acids. DDA was then converted to functionalized lipids by the Michael addition and Heck reaction. The Michael addition of thiophenol and 4-bromothiophenol yielded the corresponding linear thioethers whereas and Heck reaction products from bromobenzene and bromoanisole yielded triacylglycerols containing trans-cinnamic acid and trans-(4-methoxy)cinnamic acid, respectively.     

Synthesis of High Refractive Index Silicone Materials Incorporating Aromatic Moieties with Adjacent Linkage Groups for Flexible Electronic Displays

The refractive index study of copoly(arylene-siloxane)s constructed with amide, ester, or ether linkage units was conducted to synthesize a step-growth polymer for application in flexible displays. The copoly(arylene-siloxane) based materials have potential use in optical applications due to their durability, flexibility, and possession of good optical clarity properties when compared to conventional silica-filled polydimethylsiloxane-based materials. Measurement of refractive index (RI) was used as the main mode of analysis due to its direct correlation to optical clarity and material flexibility. Synthesis and characterization, including RI compiled data, was performed for six series of step-growth polymers. Effects of different linkage units, namely amides, esters, and ethers, adjacent to at least one six-membered cyclic unit (aromatic or aliphatic) were evaluated. It was observed that the refractive index of these polymers was directly proportional to the aryl content; however, the influence on RI was not equal across all types of linkage units. The highest RI copolymer, poly(4,4-methylenediphenyl diisocyanate-co-carbinol-terminated polydimethylsiloxane) (MDI-SD1.0k), yielded refractive index 1.470 and molecular weight (M_n) 16,100 g/mol; however, the copolymer poly(toluene-2,4-diisocyanate-co-carbinol-terminated polydimethylsiloxane) (TDI-SD) had the highest RI (1.462) per phenyl content. The 4,4-methylenediphenyl diisocyanate (MDI), toluene-2,4-diisocyanate (TDI), and hydrogenated methylenediphenyl-4,4-diisocyanate (HMDI) amide containing linkages best improved the refractive indices of the materials studied.     

Modifications to methods for the enumeration and detection of injured Escherichia coli O157:H7 in foods

Reliable methods are required for the detection and enumeration of potentially injured E. coli O157 in food in the presence of outnumbering competing bacteria. Selective agents can prevent or inhibit the recovery and subsequent multiplication of injured cells and direct inoculation, either into selective enrichment broths or onto selective agar plates is still used in many methods for E. coli O157 detection and enumeration. When compared with tryptone soya agar (TSA), sorbitol MacConkey agar (SMAC) was shown to underestimate the concentration of viable E. coli O157:H7 subjected to low pH and high NaCl concentration. Using a resuscitation stage on TSA followed by membrane transfer to SMAC improved recovery to levels obtained on TSA. The membrane method was used to monitor the numbers of artificially contaminated E. coli O157:H7 during the fermentation of a meat product and demonstrated better survival when compared to counts on SMAC. Six rapid methods for the detection of E. coli O157 in food (BAX E. coli O157, Reveal 8 E. coli O157-H7 screening test, VIP EHEC, VIDAS E. coli O157 (ECO), EHEC-Tek and Tecra E. coli O157 visual immunoassay), were evaluated using beetburgers, parsley and fermented meat artificially contaminated with injured cells. Methods using direct selective enrichment, with or without an elevated incubation temperature gave false-negative results. The incorporation of a non-selective pre-enrichment medium improved the detection rates of these assays by up to ten fold.     

Cyclic-3',5'-nucleotide phosphodiesterase isozymes in cell biology and pathophysiology of the kidney

Investigations of recent years revealed that isozymes of cyclic-3', 5'-nucleotide phosphodiesterase (PDE) are a critically important component of the cyclic-3',5'-adenosine monophosphate (cAMP) protein kinase A (PKA) signaling pathway. The superfamily of cyclic-3', 5'-phosphodiesterase (PDE) isozymes consists of at least nine gene families (types): PDE1 to PDE9. Some PDE families are very diverse and consist of several subtypes and numerous PDE isoform-splice variants. PDE isozymes differ in molecular structure, catalytic properties, intracellular regulation and location, and sensitivity to selective inhibitors, as well as differential expression in various cell types. A number of type-specific "second-generation" PDE inhibitors have been developed. Current evidence indicates that PDE isozymes play a role in several pathobiologic processes in kidney cells. In rat mesangial cells, PDE3 and PDE4 compartmentalize cAMP signaling to the PDE3-linked cAMP-PKA pathway that modulates mitogenesis and PDE4-linked cAMP-PKA pathway that modulates generation of reactive oxygen species. Administration of selective PDE isozyme inhibitors in vivo suppresses proteinuria and pathologic changes in experimental anti-Thy-1.1 mesangial proliferative glomerulonephritis in rats. Increased activity of PDE5 (and perhaps also PDE9) in glomeruli and in cells of collecting ducts in sodium-retaining states, such as nephrotic syndrome, accounts for renal resistance to atriopeptin; diminished ability to excrete sodium can be corrected by administration of the selective PDE5 inhibitor zaprinast. Anomalously high PDE4 activity in collecting ducts is a basis of unresponsiveness to vasopressin in mice with hereditary nephrogenic diabetes insipidus. Apparently, PDE isozymes apparently also play an important role in the pathogenesis of acute renal failure of different origins. Administration of PDE isozyme-selective inhibitors suppresses some components of immune responses to allograft transplant and improves preservation and survival of transplanted organ. PDE isozymes are a target for action of numerous novel selective PDE inhibitors, which are key components in the design of novel "signal transduction" pharmacotherapies of kidney diseases.