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Biomedical subjects

S R Nelson

Publications and source records attributed to S R Nelson.

At least 73 records · Page 4Linked to original sources

Soman-induced brain lesions demonstrated by muscarinic receptor autoradiography.

Repeated exposure of rats to sublethal doses of soman resulted in moderate to severe symptoms of anticholinesterase intoxication and a pronounced weight loss within a small subgroup of these animals. A consistent pattern of cell loss and extensive neuronal necrosis appeared in specific brain areas within this subgroup. This neuropathology was not noted in rats unless they showed marked symptoms of poisoning including a precipitous weight loss. Neuropathology was most notable in the piriform cortex and thalamus. Quantitative receptor autoradiography indicated that these subjects had a significant decrease in muscarinic receptors in the piriform cortex and thalamus. The ratio of the muscarinic receptor densities in soman-treated rats with lesions to soman-treated rats without lesions was 57%, piriform cortex; 64%, ventrolateral thalamus; and 50%, mediodorsal thalamus. These decrements are distinguished from adaptive down-regulation because they are larger, there is no indication of recovery and there is a correspondence between histological lesions and the areas with decreases in muscarinic receptors. Thus, quantitative receptor autoradiography provides, in addition to kinetic information and topographical distribution, radiohistochemical evidence of neuronal damage.

Animals↗

Soman induced changes in brain regional glucose use.

Soman, a potent central acetylcholine esterase inhibitor, has a greater impact on brain regional glucose use than other organophosphates, such as diisopropylfluorophosphate (DFP) or phospholinium iodide. At near-lethal doses soman induced explosive persistent seizures that were associated with a greater than fourfold increase of glucose use in many brain structures. Single near-lethal doses of soman lead to conspicuous neuronal damage and a marked reduction in brain activity, 1 to 3 days after exposure. When soman (2 X LD50) was given to TAB (an antidotal mixture of trimedoxime, atropine, and benactyzine ) pretreated rats, there was a greater than twofold reduction of glucose use in almost every brain region. We suggest that soman seizures are mediated via activation of muscarinic receptors; also, the substantia nigra has a key role in the initiation/propagation of seizures. Soman has in addition, a depressive effect on some brain components which appears not to involve muscarinic receptors. We suggest that the conspicuous pathology that follows a single, near-lethal dose of soman results from a depletion of energy flow along with an influx of Ca2+ which sets into motion a cascade of destructive reactions, such as activation of proteases.

Animals↗

Topographical distribution of down-regulated muscarinic receptors in rat brains after repeated exposure to diisopropyl phosphorofluoridate.

Quantitative receptor autoradiography demonstrated that muscarinic receptors were down-regulated in Wistar rats after repeated exposure to diisopropyl phosphorofluoridate. The density of receptors was decreased to 60-85% of the controls. Reductions in muscarinic receptor binding were observed in cortex, caudate-putamen, lateral septum, hippocampal formation, superior colliculus, and pons. The density of muscarinic receptors was unchanged in thalamic and hypothalamic nuclei, periaqueductal grey, cerebellum, inferior colliculus and reticular formation of the brain stem. The down-regulation of muscarinic receptors in forebrain structures, such as cortex, caudate-putamen and hippocampus, may be important in the adaptation to the behavioral effects of organophosphate poisons.

Animals↗

Hospital-sponsored group practice.

Henry Ford Hospital, a 1,000-bed institution in central Detroit, is being developed into a "center of excellence" with expansion of ambulatory care to suburban satellite clinics. A hospital-based HMO has been started in an effort to cut costs, decentralize care, and provide an alternative to Blue Cross. It has been successful and is now being considered as a solution to Michigan's Medicaid problems. Background and analysis follow.

Health Maintenance Organizations↗

Topographical distribution of decrements and recovery in muscarinic receptors from rat brains repeatedly exposed to sublethal doses of soman.

[3H]Quinuclidinyl benzilate binding to rat brain muscarinic receptors decreased after repeated exposure to soman, a potent organophosphorus cholinesterase inhibitor. The topographical distribution of this decrement was analyzed by quantitative receptor autoradiography. After 4 weeks of soman, three times a week, quinuclidinyl benzilate binding decreased to 67 to 80% of control in frontal and parietal cortex, caudate-putamen, lateral septum, hippocampal body, dentate gyrus, superior colliculus, nucleus of the fifth nerve, and central grey. Minor or no decreases were observed in thalamic or hypothalamic nuclei, reticular formation, pontine nuclei, inferior colliculus, nucleus of the seventh nerve, and cerebellum. Scatchard analyses of saturation curves using frontal cortex sections from soman-treated rats revealed a decrease in maximal quinuclidinyl benzilate binding from that in control rats and a return toward control levels by 24 days without any significant change in affinity. These brain areas showing significant decrements in muscarinic receptors recovered with a similar time course. An estimate of the time for 50% recovery for some of the brain areas was 14 days for superior colliculus, 16 days for cortex, and 19 days for hippocampal body. The application of quantitative receptor autoradiography to analyze receptor alterations has been valuable in localizing the telencephalon as a region more susceptible to change in receptor concentration.

Animals↗

Tissue freeze-drying with a closed drying tube stored in a freezer.

A simple method of freeze-drying tissue is described that does not require a continuously running vacuum pump. After the frozen tissue is positioned a few centimeters from the dessicant in a drying tube, a vacuum pump is attached briefly to lower the pressure in the drying tube. The drying tube is closed at a pressure of 5 X 10(-3) mm Hg or less, and the tube is stored in a freezer set at the desired temperature. Frog kidneys, 300-400 mg, were dry in about 24 hr at -32 degrees C and 48 hr at -40 degrees C. Since the tissue is dried in individual drying tubes, many tissue samples can be dried at one time.

Animals↗

Hypocalcemia and motor neuron degeneration in paraphysectomized frogs.

The paraphysis has been studied extensively but its function is unknown. Surgical removal of the paraphysis in the bullfrog (Rana catesbeiana) resulted in hypocalcemia and tetany in 35 frogs, about 40% of those operated upon. One or two days after the onset of tetany (about 8 days postoperative), progressive weakness was observed, beginning in the hind limbs. The caudal half of the spinal cord showed a green discoloration in afflicted frogs and histologically motor neurons in the lumbar spinal cord were swollen, indented with vacuoles, and had reduced processes. The paraphysis appears to play a role in calcium regulation in the bullfrog; the motor neuron degenerative changes observed may be secondary to the altered calcium metabolism.

Animals↗

Superior colliculus activation by retinal nicotinic ganglion cells: a 2-deoxyglucose study.

Systemic injection of the acetylcholinesterase inhibitor, di-isopropylfluorophosphate, in rats causes a marked increase in glucose use in the superficial layers of the superior colliculus. This activation of the superior colliculus is largely a retinal effect. Furthermore, since this response can be blocked by intraocular as well as systemic injections of mecamylamine, it is postulated that retinal nicotinic receptors are involved.

Animals↗

Influence of chloralose on brain regional glucose utilization.

Choralose, a widely used anesthetic in neurophysiology, produces a unique pattern of anesthesia characterized by both an excitant (myoclonic jerks and startle response) and depressant (sedation and anesthesia) action. We investigated the influence of chloralose on the rate of regional brain glucose metabolism to determine if chloralose produces anesthesia by hyperexciting certain brain regions. That is, does chloralose act as an 'epileptoid anesthetic'. Rats were anesthetized with either 60 or 120 mg/kg chloralose and regional brain glucose utilization rates quantitated by the 2-deoxyglucose method. In chloralose-anesthesized rats, glucose consumption rates decreased in the frontal and auditory cortex, reticular nucleus of thalamus, superior colliculus, medial geniculate body, midbrain reticular formation and hippocampus. Rates of glucose use were not decreased in the lateral lemniscus and a zone in the vicinity of the oculomotor nucleus, medial longitudinal fasciculus and surrounding reticular formation. Since chloralose did not induce any discernible focal points of high activity, chloralose appears not to be an epileptogen. Rather, chloralose appears to act as a general depressant except in certain gray areas of the midbrain and lower brain stem. Retained and possibly increased functional activity in the vicinity of the oculomotor nucleus and medial longitudinal fasciculus may represent active reflex pathways involved in mediating the paradoxical startle response and myoclonic activity observed in chloralose-anesthetized animals.

Analysis of Variance↗

The influence of droperidol, diazepam, and physostigmine on ketamine-induced behavior and brain regional glucose utilization in rat.

Diazepam and droperidol are used clinically with ketamine anesthesia to reduce emergence hallucinations, vivid unpleasant dreams, and hyperexcitability. Also, there are reports that the recovery time from ketamine anesthesia is shortened after administration of physostigmine. The authors investigated the influence of diazepam, droperidol, and physostigmine pretreatment on ketamine anesthesia by measuring the brain local regional activity and behavioral responses in rat. The 2-deoxyglucose brain local metabolic mapping method was used to determine regional brain functional activity. The recovery of tail flick response and righting reflex from ketamine anesthesia were prolonged by diazepam and by droperidol pretreatment, but the duration of agitation was shortened; physostigmine caused no significant change in any of these responses. Ketamine alone caused a statistically significant (P less than 0.05) increase in the rate of glucose utilization along the hippocampal molecular layer (control 87 mumol . 100 g-1 . min-1; ketamine 166 mumol . 100 g-1 . min-1) and a decrease in medial geniculate (25%), inferior colliculus (37%), and lateral habenula (18%). Diazepam, droperidol, and physostigmine pretreatment did not significantly alter any ketamine-induced glucose use changes, except for a decreased activity in hippocampal molecular layer with diazepam pretreatment (20%) and an increased activity in the lateral habenula with droperidol pretreatment (94%, P less than 0.05). These findings corroborate the "epileptogenic" character of ketamine anesthesia and implicate the hippocampus as a major focus. The reduced activity in the hippocampus induced by diazepam retreatment and the increased activity in the lateral habenula induced by droperidol pretreatment may be factors in the clinical reduction of ketamine hyperexcitability and hallucination by these drugs.

Animals↗

Ketamine-induced changes in regional glucose utilization in the rat brain.

Ketamine appears to induce both excitatory and depressant actions in the brain; however, it is not clear which regions are affected. The 2-deoxyglucose functional mapping method of Sokoloff et al. was used to determine regional variations in metabolic activity of rat brain caused by injection of ketamine, 25-75 mg, intramuscularly. To compare the effects of ketamine with those of hippocampal-induced seizures, the 2-deoxyglucose method was used, following injection of penicillin G, 400-800 units, into the hippocampus. The findings from five control, seven ketamine-treated, and three penicillin G-treated rats are given. Ketamine caused a significant increase of metabolic activity in the hippocampal sulci and a decrease of activity in the medial geniculate and the inferior colliculus. Similar changes were found with hippocampal seizures caused by penicillin. The inhibition of the regions associated with sensory systems (medial geniculate and inferior colliculus) may account in part for the anesthetic action of ketamine, while the intense activity of the hippocampus may be related to the excitatory manifestations. The results indicate that ketamine produces seizures in the hippocampus, which in turn inhibit auditory and visually associated nuclei. Thus, the anesthesia may follow from the sensory depression and the cataleptic phenomena may be related to the hippocampal excitation.

Animals↗

Acute effects of an aerosol hair spray on tracheal mucociliary transport.

The acute effects of a commercially available aerosol hair spray preparation and a Freon propellant on various pulmonary function tests and tracheal mucociliary transport were studied in 12 normal nonsmokers. Tracheal mucous velocity was estimated by a roentgenographic method. In 7 subjects exposed to hair spray by directing the aerosol to the hair for 20 sec, no significant changes occurred in any of the various pulmonary function parameters, whereas mean tracheal mucous velocity decreased by 57 per cent (P less than 0.001) 1 hour after exposure. This effect was transient and could no longer be demonstrated after 3 hours. No significant changes in tracheal mucous velocity or pulmonary function tests were observed in the 5 control subjects exposed to the Freon propellant alone. These observations suggest that acute exposure to aerosol hair spray produces a transient impairment of a pulmonary defense mechanism, and that measurements of mucociliary transport is a more sensitive indicator of this type of airway irritation than conventional pulmonary function tests.

Adult↗