Implantable hearing device performance measured by laser Doppler interferometry

Recent application of the Doppler principle laser interferometry to audiology, acoustics and otology has facilitated the development of implantable hearing devices (IHDs). During the design and testing of two different electromagnetic middle ear implants for sensorineural hearing loss, we used single-point laser Doppler interferometry (LDI). A commercially available interferometer, internally calibrated and validated against a National Institute for Standards and Technology (NIST) standard, was used with both mechanical fixtures and fresh temporal bones to evaluate implant mass, shape and orientation, attachment, electromagnetic coupling and acoustic properties. At both Hough Ear Institute and Symphonix Devices, Inc., we have shown that high fidelity and amplitudes can be recorded in vitro over a frequency range of 500 Hz to 10 kHz. These data can provide greater assurance of safety and efficacy to regulatory agencies before entering clinical trials. We propose that LDI be considered as an international standard for accurate, consistent comparison of performances of all IHDs during development. Furthermore, the future availability of human IHD data will allow for the extrapolation of a mechanical bench model of the middle ear transfer function for use in quality control during manufacturing and diagnosis of failure in IHDs.     

Mutations in rotavirus nonstructural glycoprotein NSP4 are associated with altered virus virulence

Rotaviruses are major pathogens causing life-threatening dehydrating gastroenteritis in children and animals. One of the nonstructural proteins, NSP4 (encoded by gene 10), is a transmembrane, endoplasmic reticulum-specific glycoprotein. Recently, our laboratory has shown that NSP4 causes diarrhea in 6- to 10-day-old mice by functioning as an enterotoxin. To confirm the role of NSP4 in rotavirus pathogenesis, we sequenced gene 10 from two pairs of virulent and attenuated porcine rotaviruses, the OSU and Gottfried strains. Comparisons of the NSP4 sequences from these two pairs of rotaviruses suggested that structural changes between amino acids (aa) 131 and 140 are important in pathogenesis. We next expressed the cloned gene 10 from the OSU virulent (OSU-v) and OSU attenuated (OSU-a) viruses by using the baculovirus expression system and compared the biological activities of the purified proteins. NSP4 from OSU-v virus increased intracellular calcium levels over 10-fold in intestinal cells when added exogenously and 6-fold in insect cells when expressed endogenously, whereas NSP4 from OSU-a virus had little effect. NSP4 from OSU-v caused diarrhea in 13 of 23 neonatal mice, while NSP4 from OSU-a caused disease in only 4 of 25 mice (P < 0.01). These results suggest that avirulence is associated with mutations in NSP4. Results from site-directed mutational analyses showed that mutated OSU-v NSP4 with deletion or substitutions in the region of aa 131 to 140 lost its ability to increase intracellular calcium levels and to induce diarrhea in neonatal mice, confirming the importance of amino acid changes from OSU-v NSP4 to OSU-a NSP4 in the alteration of virus virulence.     

Nephrotoxic potential of 2-amino-5-chlorophenol and 4-amino-3-chlorophenol in Fischer 344 rats: comparisons with 2- and 4-chloroaniline and 2- and 4-aminophenol

Nephrotoxicity occurs following intraperitoneal (i.p.) administration of 2-chloroaniline or 4-chloroaniline hydrochloride to Fischer 344 rats, but the nephrotoxicant chemical species and mechanism of nephrotoxicity are unknown. The purpose of this study was to evaluate the in vivo and in vitro nephrotoxic potential of 2-amino-5-chlorophenol and 4-amino-3-chlorophenol, metabolites of 4-chloroaniline and 2-chloroaniline. A comparison was also made between the nephrotoxic potential of the aminochlorophenols and the corresponding aminophenols to examine the effect of adding a chloride group on the nephrotoxic potential of the animophenols. Male Fischer 344 rats (4/group) were given an i.p. injection of a chloroaniline or aminochlorophenol hydrochloride (1.5 mmol/kg), and aminophenol (1.0 or 1.5 mmol/kg), or vehicle, and renal function monitored at 24 and 48 h. Both aminochlorophenols induced smaller and fewer renal effects that the parent chloroanilenes in vivo. Also, 4-aminophenol was markedly more potent as a nephrotoxicant that 4-amino-3-chlorophenol, while 2-aminophenol and 2-amino-5-chlorophenol induced only mild change in renal function. In vitro, the phenolic compounds reduce p-aminohippurate accumulation by renal cortical slices at bath concentrations of 0.01 mM, while a bath concentration of 0.50 mM or greater was required for the chloroanilines. However, all compounds reduced tetraethylammonium accumulation at bath concentrations of 0.1-0.5 mM or greater. These results indicate that extrarenally-produced aminochlorophenol metabolites do not contribute to the mechanism of chloroaniline nephrotoxicity. Also, the reduced nephrotoxic potential of 4-amino-3-chlorophenol compared to 4-aminophenol could result from an altered ability of the aminochlorophenol to redox cycle or form conjugates.     

Hydrogenation of Tasmanian alginite — analysis of hexane-soluble products by thermal distillation-gas chromatography-mass spectrometry

The liquefaction of coals and oil shales has the potential to provide a valuable alternative source of liquid hydrocarbons. Characterization of the products from liquefaction studies provides information on the nature of the hydrocarbons formed from various source materials and hence on their potential usefulness as alternative sources of liquid fuels. This paper reports a study of the nature of the hexane-soluble hydrocarbons derived from the hydrogenation of an alginite concentrate of Tasmanites sp. Characterization of these mixtures has been achieved by thermal distillation (TD) combined with computerized gas chromatography-mass spectrometry (c-g.c.-m.s.). With increase in the temperature of hydrogenation a decrease in the relative concentration of tricyclic diterpenoids is observed. At the same time there is an increase in the concentration of tricyclic aromatic compounds. The presence of the metal halide catalysts, zinc chloride and tin(II) chloride, reduces the temperature at which the elimination or aromatization of the diterpenoid compounds occurs.     

On the synergistic effects of abrasion and corrosion during wear

The interactive effects of abrasion and corrosion were studied as a function of abrasive load, corrosion time and the frequency of abrasive and corrosive treatments. The initial rate of corrosion is independent of abrasive load but the percentage contribution to wear of corrosion decreases with increasing abrasive load. It has also been found that increasing the frequency of exposure to abrasion and corrosion increases the wear loss for a constant total amount of abrasion and corrosion. These effects are discussed in terms of the nature of the work-hardened surface layer and the chemical activity of this layer.     

The in-vitro digestibility of feedstuffs–a century of ferment

The origins and development of in-vitro techniques for the determination of the apparent digestibility of ruminant feedstuffs are critically reviewed. Special attention is given to the effect of the pH used for the pepsin digestion stage, its optimum value, and its solubilising effect upon various mineral compounds and protein- and mineral-tannin complexes formed in the ruminant digestive system. New experimental evidence is presented concerning the latter effect. Comparisons are made with the Tilley and Terry method in widespread use at the present time.