Specifity and sensitivity of the inhibition of drug metabolism following inhalation of carbon disulphide-air mixtures.

A single 8-h exposure of adult female Wistar rats to 20 ppm carbon disulphide (CS2), the threshold limit value (TLV) in several countries, was sufficient to cause inhibition of the following drug-metabolizing reactions: formation of trichloroethanol and trichloroacetic acid from trichloroethylene (aliphatic C-hydroxylation), formation of 4-hydroxyantipyrine from antipyrine (quasi-aromatic C-hydroxylation), formation of acetaminophenol from acetanilid (aromatic C-hydroxylation) and phenacetin (oxidative odealkylation), respectively, and formation of 4-aminoantipyrine from aminopyrine (oxidative N-demethylation). The behaviour of these effects was dependent on the dose of CS2 administered in that the inhibitory process was enhanced when increasing the concentration to (50), 100, 200, and 400 ppm. The respective changes could be demonstrated by a short-duration (6-h) reduction in the urinary excretion of the metabolites. In the case of trichloroethylene the limitation in metabolite formation persisted for as long as 36 h due to the varying rate of formation of trichloroethanol and trichloroacetic acid. This deficiency in excretion was compensated in part during the subsequent elimination phase (up to 24 and 36 h, respectively), an observation which suggests the rapid reversibility of the alteration. As shown by the respective prolongation of the hexobarbital sleeping time in the rat, the side-chain oxidation of hexobarbital to ketohexobarbital was increasingly inhibited by rising concentrations of CS2 in the range of 20 to 400 ppm/8 h. On the basis of the present results it is concluded that CS2 also inhibits various oxygenases of the microsomal enzyme system. In adult female NMRI mice a significant inhibition of the microsomal procaine-hydrolyzing esterase of the liver was observed only after 400 ppm/8 h; however, this limitation did not affect the LD50 of procaine-HCl, particularly as the corresponding serum esterase activity also remained uninfluenced. The aromatic N-acetylation of sulphisomidine and the quasi-aromatic N-acetylation of 4-aminoantipyrine in rats failed to be significantly reduced by CS2 even after 400 ppm/8 h, nor did the same dose of CS2 affect the glucuronidation of 4-hydroxyantipyrine in the same animal species. It is concluded from the above results that the specificity and sensitivity of the inhibition of drug metabolism observed in small laboratory animals is probably similar to that prevailing in man. This assumption has already been substantiated for the oxidative N-demethylation of aminopyrine.

Thin slits: transmission and polarization.

The paper discusses measurement of the transmission ratio T ||/T? of thin slits for light polarized linearly parallel and perpendicular to the slit direction at optical wavelengths and as a function of the angle of incidence. To obtain perfectly identical geometrical beams, the plane of polarization of the linearly polarized light is rotated in the measuring setup by means of plates of optically active quartz. The results indicate that the transmissivity is higher for light polarized parallel to the slit direction. This effect is more pronounced with narrow slits than with wide slits and, moreover, increases with the wavelength. For tangential orientation of the slit, the ratio T ||/T? increases with the angle of incidence. The paper studies the effect of surface reflections.

Focusing Criterion for Ground-Glass-Focused Lenses, Derived from MTF Measurements.

Lenses used in the graphic arts and in professional photography generally are focused on a ground-glass screen. In order to obtain a mathematically defined focusing criterion, a sector star target was visually focused on a ground glass through several of these lenses and the MTF curves measured at various receiving planes. It was found that in the frequency range between 15 cycles/mm and 30 cycles/mm the visual receiving plane gives higher MTF values than in any other plane. The corresponding contrast values were found to lie between 0.3 and 0.5.

Modulation transfer functions of ground-glass screens.

The modulation transfer functions of different ground-glass screens produced by grinding or etching can be measured. Since screens of this type destroy the coherence of an optical beam, their transfer function can be measured by determining first the transfer function L(0)(f) of an auxiliary lens including a planeparallel plate directly in front of the image plane, designed to simulate the ground-glass thickness, and then the transfer function L(1)(f) of the auxiliary lens including the ground glass placed directly in front of the image plane. The transfer function of the ground glass is then given by the quotient L(1)(f)/L(0)(f).

An instrument for determining the transfer function of optical systems.

The paper describes an instrument for measuring the transfer function of optical systems. The test object used is a very narrow slit. The fine-line image produced by optical image formation is measured without a microscope objective, whereupon the optical transfer function is computed with the aid of an analog computer. The highest frequency to be measured is 750 cycles/mm. The instrument is suited for any scale of reproduction and allows measurement of the fine-line image, the optical transfer function, the knifeedge image, and vignetting.