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Biomedical subjects

S Norton

Publications and source records attributed to S Norton.

At least 73 records · Page 4Linked to original sources

Drug withdrawal prior to hatch in the morphine tolerant chick embryo.

Morphine tolerance and dependence were produced in chick embryos by injecting 20 mg/kg into the air space of the egg daily from incubation day 12. Starting on day 16, two groups of eggs were withdrawn from morphine by either substituting water or by treating with naloxone. Chick embryo activities were monitored on incubation day 18. Activities of the embryos withdrawn from morphine did not differ from control, but naloxone injection produced a substantial increase in activity. Neither regimen of morphine withdrawal affected the hatchability of the eggs. When these chicks were 1 day old, the effect of 1 mg morphine/kg on the rate of distress vocalization was measured. The withdrawn chicks were 1 day old, the effect of 1 mg morphine/kg on the rate of distress vocalization was measured. The withdrawn chicks vocalized at a rate that was intermediate between that of controls and that of nonwithdrawn chicks indicating that tolerance was still present one week after the last morphine injection.

Animals↗

Relationship of dose to morphine tolerance in the chick embryo.

Morphine tolerance and dependence can be produced in chick embryos by injecting 20 mg/kg into the airspace of the egg daily for 4 days beginning on incubation day 12. The experiments in this report examined the production of tolerance with lower doses of morphine (2.5, 5.0 and 10.0 mg/kg). Treatment of embryos for 4 days did not produce tolerance on day 16 when the challenge dose was the same as the dose used for pretreatment and when activity was recorded at only one time after injection. Further studies measuring activity at multiple time-points and/or utilizing a lower challenge dose indicated that tolerance was present. Studies of activity after 4 or 8 days of pretreatment revealed a dose-effect relationship. Pretreatment with 2.5 mg/kg produced a lesser degree of tolerance than that produced by the higher pretreatment doses. These embryos were tolerant on day 16 after four injections but not on day 19 after eight injections, due perhaps to more rapid metabolism of morphine with age. There were no differences between the responses of the 5.0 and 10.0 mg/kg groups to morphine challenge. While both of these doses produced tolerance to a low challenge dose of morphine by day 16, pretreatment at doses higher than 10.0 mg/kg was necessary for production of tolerance to high doses.

Animals↗

The pyramidal neuron in cerebral cortex following prenatal X-irradiation.

Pregnant rats were subjected to whole body X-irradiation amounting to 125 R, on gestational day 15. Cortical pyramidal neurons were examined in irradiated and control offspring at 4 weeks and 4 to 6 months postnatally. All gestationally irradiated rats developed ectopic cortex located below the corpus callosum adjacent to the caudate nucleus in the forebrain. With the rapid Golgi stain, counts were made of dendritic spines on the apical dendrites of layer 5 pyramidal cells in the normally-located cortex and compared with similar neurons in the ectopias. Dendritic spines were present on all pyramidal cells but spines were more sparse on ectopic pyramidal cells. Electron microscopic examination of ectopic and layered cortex in irradiated rats showed axodendritic synapses on the spines and shafts of the dendrites and axosomatic synapses, all of which were indistinguishable morphologically from synapses in control cortex. As a result of the observations made with the light and electron microscopes, it is concluded that the ectopic cortex may contain functional cells in spite of the abnormal location of the tissue.

Age Factors↗

Development of opiate tolerance in the chick embryo.

Tolerance to morphine was produced in the chick embryo. Eggs were injected with morphine sulfate (MS) (20 mg/kg egg) or H2O daily starting on incubation day 12. On day 16, embryo activities were recorded and eggs were injected with either MS or naloxone. Activity of H2O-pretreated controls decreased after both MS and naloxone. Embryos treated with MS from incubation days 12-15 showed no activity change after morphine and responded to naloxone with increases in activity. Baseline rates of distress vocalizations (DV) of 1-2 day old chicks were not affected by MS pretreatment during incubation days 12-19. However, 1 mg/kg MS decreased the rate of DV of control chicks by 90% whereas MS-pretreated chicks were unaffected. At age 4-5 days, the baseline rate of DV and rate after MS were higher in MS-pretreated chicks. However, all chicks showed significant decreases in rate of DV after MS injection. Naloxone increased the rate of DV of paired 1-2 day old chicks, but response of MS-pretreated chicks was significantly greater than controls.

Animals↗

Alterations of chick locomotion produced by morphine treatment in ovo.

Analysis of walking of young chicks showed that morphine treatment of the chick embryo resulted in motor difficulties that depended on the timing of initial morphine exposure. Morphine sulfate was injected daily at a dose of 20 mg/kg egg into the air sac of viable eggs. Groups of eggs were treated starting on either day 12 or day 16 of incubation with either morphine or sterile water. Injections were continued through incubation day 19 and the eggs were allowed to hatch. The chicks started on morphine on day 16 showed signs of neuromuscular weakness at the posthatching age of 1-2 days. At 7 days of age they had a wider stride and greater angle of placement of the feet compared to both the controls, and to the chicks that were started on morphine on day 12. Since tolerance to morphine can develop in the chick embryo after only 4 daily injections, the chicks receiving morphine from day 12 may have been tolerant to the deleterious effects produced by morphine on locomotion at a critical period of motor development around day 16.

Animals↗

Neuronal damage in chick and rat embryos following X-irradiation.

Exposure of rat and chick embryos to X-irradiation at the time of development of neurons at the telencephalic-diencephalic border results in prolonged damage to neurons in this area as measured by neuronal nuclear size. A dose of 100 rads to the seven-day-old chick embryo has about the same effect as 125 rads to the 15-day-old rat fetus. The nuclear volume of large, multipolar neurons in the chick paleostriatum primitivum and the rat lateral preoptic area are reduced from 10 to 15%. Larger doses of X-irradiation to the chick (150 and 200 rads) cause progressively greater reductions in nuclear size. The large neurons which were measured in the rat and chick are morphologically similar in the two species. Both contain cytoplasmic acetylcholinesterase and have several branched, spiny dendritic processes. The similarity of response of chick and rat neurons to X-irradiation diminishes the significance of maternal factors as the cause of the effects of fetal irradiation in these experiments.

Animals↗

Selective hearing screening for young children.

A "selective" hearing screening program was instituted in an early education project. Three-year-old children were deemed "at risk" for mild-to-moderate hearing loss if they met one of the risk criteria established by the Joint Committee on Infant Hearing Screening, if they had recurrent ear infections, or if there was parent or staff concern about the child's hearing. Based on these criteria, 31 per cent of the 228 children in the project were eligible for full audiologic evaluation at a speech and hearing center. The parents of 45 children took advantage of this special evaluation. Twenty-nine per cent of these selected children had some hearing loss documented. The highest yields of abnormal hearing were for children "at risk" because of recurrent ear infections (42%), and parent for educational staff concern (71%).

Child↗

Equivalent ages in rat, mouse and chick embryos.

Data for estimating equivalent ages of rat, mouse and chick embryos are presented, using several sources from the literature. When the time of development of various embryonic structures is matched for the three species, the differences in time for the stages are primarily due to delays in development of the preimplantation blastulas of the rat and mouse in comparison with the incubated chick egg. Development from the blastula stage to completion of major organogenesis proceeds at approximately the same rate for all three species.

Animals↗

Development of rat telencephalic neurons after prenatal X-irradiation.

Telencephalic neurons of rats, irradiated at day 15 of gestation with 125 R, develop synaptic connections on dendrites during maturation which appear to be normal spines in Golgi-stained light microscope preparations. At six weeks of postnatal age both control and irradiated rats have spiny dendritic processes on cortical pyramidal cells and caudate Golgi type II neurons. However, when the rats are 6 months old the irradiated rats have more neurons with beaded dendritic processes that lack spines or have only a few spines. These neurons resemble the neonatal neurons and are likely to be degenerating neurons. The apparently normal development of the neurons followed by degeneration in the irradiated rat has a parallel in previous reports of the delayed hyperactivity which develops in rats irradiated on the fifteenth gestational day.

Animals↗

Postnatal behavioral changes in prenatally irradiated rats.

Rats were exposed on gestational day 15 to 125 r X-irradiation, a treatment known to severely alter brain morphology. At 4-6 weeks of age the behavior of these animals was studied using two methods: (1) measurement of circadian locomotor activity, (2) photographic analysis of behavioral acts. The circadian locomotor activity of irradiated rats was similar to that of controls tested individually or as groups in a residential unit. After morphine sulfate, 2 mg/kg, the increase in locomotor activity was greater for the irradiated than control groups. Successive frames of photographic film were analyzed to determine the frequency, duration, sequencing of behavioral acts. No significant differences were present in these parameters of behavioral acts of control and irradiated rats. After morphine, irradiated rats showed a greater increase than controls in frequency and initiations of some behavioral acts, and these acts were more randomly dispersed in the sequences of acts. In this experiment activity was little affected by an agent which severely alters brain morphology, but the latent behavioral effects of the permanent brain damage became manifest, when the testing situation included challenge with a low dose of a drug which caused hyperactivity.

Animals↗

Ototoxicity of gentamicin: clinical experience in a children's hospital.

In a effort to estimate the incidence of clinical ototoxicity in children we reviewed the charts of 374 patients who had serum gentamicin concentration determined 30 min before ('trough value') and at the pharmacologic peak after parenteral administration. 37 of these patients, between 9 and 17 years of age, had two or more audiograms; of these, 9 developed objective evidence of hearing loss; in 2 the impairment was severe and permanent. Risk factors associated with ototoxicity were renal failure, concomitant administration of diuretics and peak serum concentrations greater than 12 microgram/ml (all significant at p less than 0.01). The minimum incidence of overt hearing loss secondary to gentamicin therapy is approximately 2.4%.

Adolescent↗

Is behavior or morphology a more sensitive indicator of central nervous system toxicity?

Both behavior and morphology can be altered by exposure of the CNS to toxic substances. The brain is an organ with considerable structural redundancy and this presumably accounts for some of the ability of the CNS to maintain normal function in the presence of some structural damage. Compensation for damage may also occur through a form of "learning" due to the biochemical and morphological plasticity of the CNS. Examples of these kinds of compensation are enzyme induction and axonal sprouting. Compensatory changes such as these are likely to require days or weeks to develop. On the other hand, short-term, reversible effects of substances such as drugs are not likely to cause morphological changes at doses which affect behavior. The importance of appropriate quantitative data on both morphology and behavior in evaluation of the CNS toxicity of substances is evident.

Animals↗

A Golgi analysis of caudate neurons in rats exposed to carbon monoxide.

Interneurons of the caudate nucleus have been reported in the literature to respond to deafferentation by reduction in dendritic spines. In the studies reported here, caudate interneurons have been examined using the Golgi technique and increased numbers of spines were found in adult rats exposed to carbon monoxide as neonates. The development of spines on the caudate neurons was delayed for several days after an acute anoxic episode in 5-day-old rats exposed to carbon monoxide to the point of respiratory arrest. By the time the rats were 6 weeks old the caudate neurons had recovered to the point where they had essentially normal numbers of spines. At later ages (2- and 7-months old) the number of spines was greater in rats exposed perinatally to carbon monoxide than in control rats of the same age. The development of abnormal numbers of spines coincided with the time of recovery of rats from behavioral hyperactivity induced by carbon monoxide. The increased spines on the caudate neurons of the adult rats (7-months old) can be explained as a compensatory response to increased afferent flow to the caudate during the period of juvenile hyperactivity which reaches a peak at 6 weeks of age. It is proposed that the return to normal activity in the adult may be a consequence of increased activity of the caudate nucleus.

Age Factors↗