Neurotoxic mechanism of cinnabar and mercuric sulfide on the vestibulo-ocular reflex system of guinea pigs.

Cinnabar, a naturally occurring mercuric sulfide (HgS), has been combined with Chinese herbal medicine as a sedative for more than 2000 years. To date, its neurotoxic effect on the vestibulo-ocular reflex (VOR) system has not been reported. By means of a caloric test coupled with electronystagmographic recordings, the effect of commercial HgS and cinnabar on the VOR system of guinea pigs was studied. HgS or cinnabar was administered orally (1.0 g/kg) to Hartley-strain guinea pigs once daily for 7 consecutive days. A battery of electrophysiological, biochemical, and histopathological examinations were performed. The results showed that HgS induced a 60% caloric response abnormality (40% caloric hyperfunction and 20% hypofunction), whereas the abnormal responses appeared to be more severe (six out of six) in the cinnabar group. The Hg contents of whole blood and cerebellum were increased and correlated to their neurotoxic effects on the VOR system, indicating that both insoluble HgS and cinnabar could be absorbed from the gastrointestinal tract and distributed to the cerebellum. Although the vestibular labyrinth revealed no remarkable change under light microscopy, loss of Purkinje cells in the cerebellum was detected, and the enzymatic Na(+)/K(+)-ATPase activity of cerebellum (a higher inhibitory center of the VOR system) was significantly inhibited by HgS and cinnabar. Moreover, cerebellar nitric oxide (NO) production was increased significantly. Hence, we tentatively conclude that the increased Hg contents in the cerebellum following oral administration of HgS and cinnabar were responsible, at least in part, for the detrimental neurotoxic effect on the VOR system. Potentially, decreasing Na(+)/K(+)-ATPase activity and increasing NO production within the cerebellar regulatory center are postulated to mediate this VOR dysfunction caused by the mercurial compounds and cinnabar.

The vibration pattern of the hearing organ in the waltzing guinea-pig measured using laser heterodyne interferometry.

The mechanical tuning characteristics of the hearing organ were measured in response to sound stimulation using laser heterodyne interferometry in in vitro preparations of temporal bones from waltzing guinea-pigs expressing different degrees of hearing organ and sensory cell degeneration. Measurements were made at various stages of structural changes allowing us to correlate structure and mechanical function. It was found that the characteristic frequency of the response at a given location in the cochlea occurred at lower frequencies than what is normally seen and that the sharpness of the mechanical tuning was considerably reduced when sensory hair cells were absent and the hearing organ structurally altered. However, even when extensive hair cell degeneration was evident a residual mechanical tuning was present. These results further support the concept that the sensory hair cells plays a key role in determining normal auditory tuning characteristics. It is suggested that the basilar membrane mechanics gives rise to a broadly tuned mechanical response on which a sharper tuning mechanism, originating from the hair cells, is superimposed.

Depletion of cortical cholecystokinin levels after excitotoxin injection into the nucleus basalis: sensitivity to MK-801.

The release of cholecystokinin (CCK) in vitro has been shown to be influenced by NMDA receptors. In this study we have investigated whether excitotoxin-induced seizure activity affects the release and tissue content of CCK. Excitotoxin injection caused a significant decrease in CCK in ipsilateral frontal, parietal and temporal cortex by (30-54%) at 8 h compared to contralateral cortex and sham-operated controls and the effect was reversed by 24 h. No change was detected in occipital cortex, hippocampus and nucleus accumbens. The effect in frontal and temporal cortex was maximal at 8 h and could be completely prevented by treatment with MK-801(3 mg/kg i.p.). Anaesthesia (pentobarbital) alone or in combination with MK-801 did not affect peptide levels at 8 h. CCK mRNA levels were also studied quantitatively by slot-blot analysis but were unaffected at 6, 8 and 24 h after excitotoxin injection. The decrease in CCK tissue levels indicated that seizure activity stimulated CCK release which was confirmed in ex vivo experiments where K(+)-evoked (34 mM) CCK release was significantly enhanced in ipsilateral cerebral cortex at 6 h compared to contralateral cortex.

In vivo deterioration of proplast-teflon temporomandibular joint interpositional implants: a scanning electron microscopic and energy-dispersive X-ray analysis.

The surgical treatment of internal derangements of the temporomandibular joint (TMJ) often involves disc removal. Alloplastic interpositional implants for disc replacement have been widely used to avoid the development of osteoarthritic changes in the TMJ. This study reports the in vivo wear characteristics of Proplast-Teflon (Vitek Inc, Houston, TX) interpositional implants (PTIPI) in 12 patients who had their implants for 13 to 71 (mean 54.6 +/- 5.8 SEM) months. In all cases, changes in the condyle and fossa were found resulting from resorption and replacement of the articulating bone by granulomatous tissue. All implants showed significant signs of wear, such as thinning, cracks, and tears, and overt perforations were seen in five cases. Scanning electron microscopy (SEM) combined with energy-dispersive x-ray microanalysis (EDAX) showed numerous microfragments of the PTIPI in the peri-implant soft tissues. Microfragments were demonstrated by their aluminum content. In addition to the inflammatory foreign-body reaction, it is suggested that there also were toxic and hypersensitivity reactions to aluminum involved in the pathogenesis of the bone destruction.