[Adrenergic beta-receptor blockers--a group of chiral drugs: enantioseparation in the group of beta-blockers]. / Blokátory beta-adrenergických receptorov--skupina chirálnych lieciv: enantioseparácie v skupine beta-blokátorov.

The preparation of pure individual enantiomers represents a topical problem from the standpoint of efficacy and safety of drugs. This paper continues in the preceeding review of the blockers of beta-adrenergic receptors as a group of chiral drugs, which is concerned with different pharmacodynamic, pharmacokinetic, and toxicological effects of individual enantiomers of this group. The review paper pays attention to the problems of enantioseparation of this group of chiral drugs, listing individual examples of the methods of enantioseparation, such as crystallization, biocatalysis, chromatographic methods (HPLC, GC, TLC), capillary electrophoresis, and the method of nuclear magnetic resonance (NMR). The individual methods of enantioseparation including enantioseparation in biological material (urine, serum) are illustrated on examples on beta-blockers used in clinical practice (e.g., propranolol, atenolol, metoprolol) as well as potential agents of this group of drugs.

Inhibition of experimentally induced endolymphatic hydrops by middle ear ventilation.

The tympanic membrane was perforated (n = 19) or a tube was inserted into the middle ear through the wall of the tympanic bulla (n = 6) immediately after blockage of the endolymphatic duct in guinea pigs. Total cochlear endolymph volume and volumes in each cochlear turn were determined from serial sections of the temporal bones and volume changes were analyzed statistically by comparison with hydropic controls without treatment (n = 12). Results showed that both middle ear ventilation procedures significantly reduced the subsequent development of endolymphatic hydrops. This inhibition of hydrops was presumed to be due to pressure release into the middle ear and/or improved oxygenation of the middle and inner ears. Findings suggest the possible merit of a tympanostomy as a treatment for Meniere's disease in carefully selected patients refractory to medical management.

Vein of the vestibular aqueduct in the gerbil.

The vein of the vestibular aqueduct in the gerbil runs along the lateral side of the endolymphatic duct, deviates from this course to enter the middle ear cavity, and connects with the lateral sinus. In 20 animals, the vein of the vestibular aqueduct was obliterated by drilling from the middle ear side. Histopathology of these specimens after 2 months' survival revealed consistent sensory cell atrophy in the posterior canal cristae, frequent loss of sensory cells in a small superior portion of the macula sacculi and in the basal end of the cochlea, and fibrosis and osteogenesis in the three semicircular canals. The endolymphatic sacs contained colloidal substances in some specimens which were otherwise normal. Endolymphatic hydrops was absent except in some specimens which showed additional surgical damage to the endolymphatic sac and canals. The blocked vein re-opened occasionally and connected with the vessel formed in new bone from which it attached to the lateral sinus. The sensory cell degeneration and canal fibrosis reflects the pattern of blood drainage by the vein of the vestibular aqueduct. Vascular disorder in the vestibular labyrinth initiates vestibular symptoms; however, it will not produce endolymphatic hydrops unless function of the endolymphatic sac is impaired.

Degeneration of vestibular sensory cells caused by ablation of the vestibular aqueduct in the gerbil ear.

The vestibular aqueduct of the gerbil has a unique anatomic feature that makes it possible to selectively obliterate the endolymphatic sac with or without interfering with its venous drainage. In animals in which only the endolymphatic sac was ablated, endolymphatic hydrops was slight in the cochlea and was absent in the vestibular labyrinth. The cochlear and vestibular sensory cells were normal. In animals in which both the endolymphatic duct and the vein were obliterated, hydrops was slight, with the exception of a few cochleas that showed moderate hydrops. The sensory cells of the posterior canal cristae had degenerated in all specimens, while varied pathologic changes in cochlear and vestibular sensory cells were present in some specimens. These results suggest that hydrops is primarily due to blockage of the endolymphatic duct and sac and that degeneration of sensory cells occurs when blood flow in the vestibular aqueduct is impeded. Pathologic changes in the endolymphatic sac, including the vascular plexus at the endolymphatic sac, may play an important role in the production of endolymphatic hydrops and vestibular symptoms in Meniere's disease.

Separation of internal derangements of the temporomandibular joint using sound analysis.

This clinical-arthrographic investigation compares power spectral analysis of temporomandibular joint sounds with different arthrographic characteristics of intracapsular dysfunction. The quantitative comparison of specific parameters of the sound power-spectrum waveform may provide a sensitive and accurate noninvasive tool for diagnosis and treatment.