Anteroventral cochlear nucleus: wave forms of extracellularly recorded spike potentials.

Analysis of wave forms of spike potentials from neurons in the anteroventral cochlear nucleus indicates that the spikes are composed of three components. Two appear to be postsynaptic events, and one appears to be presynaptic and to be related to the calyces of Held found in that part of the nucleus.

Cochlear nerve fiber discharge patterns: relationship to the cochlear microphonic.

Fourier analysis of discharge patterns in response to sinusoidal acoustic stimulation provides a consistent and repeatable measure of response phase and amplitude. The variation of the fundamental and harmonic components of the patterns as stimulus parameters are changed is strikingly similar to that of cochlear microphonics. The results are significantly different for single fibers with different characteristic frequencies; the variations parallel those of microphonics recorded from different cochlear turns.

Analysis of solid-state Carbon-13 NMR spectra of polymorphs (benoxaprofen and nabilone) and pseudopolymorphs (cefazolin).

The solid-state 13C-NMR spectra of the polymorphs of benoxaprofen, nabilone, and cefazolin are reported using the cross-polarization/magic-angle spinning (CP/MAS) technique. In general, the spectra of the different crystal forms are different. In favorable cases the spectra of the drug in a pharmaceutical granulation can be discerned. These results provide a preliminary indication that solid-state NMR spectroscopy is a useful technique for the investigation of drug polymorphs and drugs in their dosage forms.

Effect of impurities on estradiol crystallization in a sustained-release implant.

During the development of a silicone rubber implant for the delivery of estradiol 17-beta some batches of implants made from a certain lot of commercial estradiol inexplicably developed surface crystals of estradiol after several days of storage. An impurity profile was obtained for 28 lots of estradiol by a newly developed HPLC method. One or more impurities may have had a role in the spontaneous crystal growth on the surface of the implants, because the one lot of estradiol that initially had surface crystals on aging produced acceptable implants after multiple recrystallizations. Attempts to isolate suspected impurities for characterization were unsuccessful. During the manufacture of the implants, temperatures sufficient to melt the estradiol (mp, 173-179 degrees C) were used. It was expected that, upon implant cooling, melted impure estradiol would form a thermodynamically more active (i.e., noncrystalline) physical form. This metastable form could have migrated to the implant surface, where ambient conditions favored crystallization. Because melted estradiol of a higher purity tended to crystallize more readily, it was less likely to form a glass upon cooling. The phenomenon of surface crystallization was limited to one lot of estradiol with the highest level of impurities. Data from differential scanning calorimetry studies supported this conclusion.

Solid-state investigations of erythromycin A dihydrate: structure, NMR spectroscopy, and hygroscopicity.

The crystal structures of the commercially available form of erythromycin A dihydrate and clarithromycin anhydrate, in addition to the structure of erythromycin B dihydrate, are reported in this paper. In light of the crystallographic data, analysis of the structural information provides insight into the physical properties of these pharmaceuticals. The propensity of these pharmaceuticals to form solvated structures is discussed and the hygroscopicity of erythromycin A dihydrate is investigated. Solid-state 13C NMR was used to monitor changes that occur when the dihydrate form of erythromycin A is stored under conditions of low relative humidity. Although erythromycin A dihydrate retains its crystallographic order at low humidity, as indicated by its X-ray powder diffraction pattern, the local chemical environment is dramatically influenced by the loss of the water molecules and results in dramatic changes in its solid-state 13C NMR spectrum.

Structural features of vancomycin.

Recent analytical methods have advanced knowledge of the structure of vancomycin from a description of only several molecular fragments to a complete understanding of the intact molecule. The molecular weight is 1,448. The molecule consists of a seven-membered peptide chain that is formed by parts of three phenylglycine systems, two chlorinated tyrosine units, aspartic acid, and N-methylleucine. Two ether bonds and a carbon-carbon bond join the various substituents on the peptide chain into three large rings. A disaccharide, composed of glucose and vancosamine, is also present but is not part of the cyclic structure. Details of the vancomycin structure have been related to hydrogen bonding between the antibiotic and bacterial cell-wall precursors that have a D-alanyl-D-alanine carboxyl terminus; such bonding would provide a molecular basis for the cell-wall mode of action for vancomycin. With one carboxyl, two amino, and three phenolic groups, vancomycin undergoes a variety of ionic interactions in solutions of different pH and composition.

Properties of 'two-tone inhibition' in primary auditory neurones.

1. Properties of two-tone inhibition in primary auditory neurones of cats were studied with phase-locked sound stimuli. One sound was a continuous tone at the best frequency of a given neurone, and the other, a tone burst which was changed in amplitude, frequency, and phase relative to the continuous tone.2. The tone burst which caused two-tone inhibition had either an excitatory or no effect when it was delivered alone. Inhibitory areas commonly appeared on both sides of the excitatory area when the best frequency was higher than a few kc/s.3. Two-tone inhibition began and ceased within a few milliseconds of the onset and termination of the excitation caused by a tone burst. The degree of inhibition was greatest at the beginning of the tone burst and reached a plateau within 500 msec. The discharge rate during inhibition could be lower than the rate for either tone alone or for spontaneous activity. At the termination of inhibition, prominent rebound in the discharge rate was found.4. With an increase in amplitude of a tone burst, for either a fixed or equally increased continuous tone, the discharge rate during inhibition decreased to a minimum and then began to increase. That is, the degree of inhibition was non-monotonically related to the sound level.5. Compound period histograms of discharges during inhibition showed that single neurones usually carried information about the combined wave form of the two tones. The information about each tone was, however, modified by the inhibitory phenomenon in both amplitude and phase from that indicated by the compound period histograms for the individual tones.6. Possible mechanisms and functional significance of two-tone inhibition are discussed.

Solid-state chemistry and crystal structure of cefaclor dihydrate.

Cefaclor [7-(D-2-amino-2-phenylacetamido)-3-chloro-3-cepham-4-carboxy lic acid] crystallizes as the dihydrate. Crystals belong to space group P21, with a = 10.626(3), b = 7.1288(9), c = 14.124(3), and beta = 121.6(2). The structure was solved using direct methods and refined to an R of 0.0535. The bond lengths, angles, and conformation determined are as expected for cephalosporins. The two water molecules are held in the crystal differently. The 13C solid-state NMR spectrum of cefaclor dihydrate is also reported and is consistent with its crystal structure.

Stable antibiotic sensitivity disks.

Two methods of preparing sensitivity disks were compared for their effect on disk stability at 25 and 37 C. One method consisted of applying a solution of the antibiotic to blank disks by the conventional procedure; the second method consisted of applying the antibiotic to the disks as a suspension of crystals. Of the four beta-lactam antibiotics that were studied, disks made with suspended crystals were substantially more stable than corresponding disks made by the conventional method. The increased stability is related to the greater chemical stability of the antibiotics in the crystalline versus the amorphous state.

The solid-state decarboxylation of the diammonium salt of moxalactam.

This paper reports studies of the solid-state chemistry of the diammonium salt of moxalactam. The methods employed include X-ray crystallography, molecular mechanics calculations, thermogravimetric analysis, and high-pressure liquid chromatography. The crystal structure shows that the malonic acid amide functionality in crystals of the diammonium salt is not planar. If the common decarboxylation mechanism is operating, then considerable rotation would be required for this functionality to attain coplanarity. Simultaneous HPLC and thermogravimetric analysis studies indicate that the decarboxylation of the diammonium salt of moxalactam is preceded by desolvation. Molecular mechanics calculations indicate that the barrier to rotation of the malonic acid amide functionality is relatively small in the dehydrated crystals, perhaps explaining the facile decarboxylation of this antibiotic. Alternatively, the amorphous desolvated crystals may allow enough molecular freedom for the malonic acid amide functionality to attain coplanarity and decarboxylate.