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Biomedical subjects

G Crosby

Publications and source records attributed to G Crosby.

44 records · Page 3Linked to original sources

Characterization of the binding of 3H-SCH 23390, a selective D-1 receptor antagonist ligand, in rat striatum.

A novel benzazepine, SCH 23390, has recently been described as a very potent and selective dopamine D-1 receptor antagonist based on its potent inhibition of dopamine sensitive adenylate cyclase and its selective displacement of 3H-piflutixol from rat striatal receptor sites. In the present study, the in vitro binding of 3H-SCH 23390 to specific striatal receptor sites has been characterized. Binding was saturable and stereospecific, and the results of both saturation and competition studies are consistent with the binding of 3H-SCH 23390 to a single striatal site. A KD of 0.53 nM was obtained through Scatchard analysis. Relative potencies of a variety of neuroleptics in competing with 3H-SCH 23390 and also 3H-spiperone support an interpretation that the single site to which 3H-SCH 23390 binds is the D-1 dopamine receptor. Also, the binding capacity of 3H-SCH 23390 (69 pmoles/gm wet weight) is in agreement with published values for the binding capacities of 3H-piflutixol and 3H-flupentixol. These data, coupled with the low level of non-specific binding encountered with this radioligand (4-8% of total binding at normally employed ligand concentration of 0.3 nM), its high specific activity and its negligible binding to plastic and glass surfaces make it ideally suited for studying interactions with this receptor.

Animals↗

A comparison of local rates of glucose utilization in spinal cord and brain in conscious and nitrous oxide- or pentobarbital-treated rats.

Local rates of glucose utilization in the spinal cord and brain were measured with the 2-[14C]deoxyglucose method in conscious and in paralyzed and mechanically ventilated pentobarbital- or 70% nitrous oxide-treated rats. In conscious animal lumbar spinal cord glucose utilization is only 40-50% that of the cerebral cortex and shows little laminar heterogeneity. Pentobarbital reduces and nitrous oxide increases the cerebral glucose utilization of most structures. The effect of paralysis and nitrous oxide analgesia on lumbar spinal cord glucose utilization is quantitatively similar to that produced in brain; 15-25% increases occur in most spinal cord laminae and cerebral structures. In contrast, the 10-20% reduction in spinal cord gray matter metabolism in the paralyzed and pentobarbital-treated animals is considerably less than the 20-50% depression measured in most brain structures. From these data the authors conclude that, relative to that of most cerebral structures, spinal cord metabolism is less sensitive to depression by barbiturates and suggest that differences in the cell populations of these tissues may account partially for this observation.

Analgesia↗

Naloxone pretreatment alters the local cerebral metabolic effect of gamma-hydroxybutyrate in rats.

The effect of naloxone on gamma-hydroxybutyrate (GHB)-induced cerebral metabolic depression was studied in rats with the 2-[14C]deoxyglucose method. Naloxone pretreatment statistically significantly antagonized the cerebral metabolic effect of GHB in 10 of 38 structures examined. These results are consistent with previous data showing reversal of the dopaminergic, electroencephalographic, and behavioral effects of GHB by naloxone and suggest that some of the neuropharmacological effects of GHB are mediated by the endogenous opiate system.

Animals↗

The local metabolic effects of somatosensory stimulation in the central nervous system of rats given pentobarbital or nitrous oxide.

General anesthetics are used to eliminate perception of stimuli, yet there have been few studies of the cerebral metabolic effects of stimulation during anesthesia, and of these studies, the results are discrepant. The authors therefore applied the quantitative 2-[14C]deoxyglucose method in a study of the effects of electrical stimulations (5 volts, 0.5 ms, 10 Hz) of a rat's saphenous nerve on glucose utilization in structures of the sensory pathway after administering pentobarbital or nitrous oxide. Under both conditions, stimulation produced a 75 to 108% increase in glucose utilization in the ipsilateral dorsal horn of the spinal cord, and a 9 to 11% increase in only a small fraction of the contralateral somatosensory cortex. No unilateral metabolic effect was seen in the dorsal column nuclei, ventroposterolateral thalamus, periaqueductal gray matter, dorsal raphe nuclei, or the reticular formation. The results of this study show that during peripheral stimulation, little metabolic response is seen in the brain even if the animal is receiving only nitrous oxide (70%), while the dorsal horn of the cord responds dramatically under the same conditions. Moreover, anesthesia with the potent cerebral metabolic depressant pentobarbital does not substantially alter the metabolic responsiveness of the cord or brain to stimulation. Thus, although there are marked differences between the rest in rate of metabolism produced by 70% nitrous oxide and pentobarbital, in terms of their effects on the metabolic response to stimulation, the agents are quite similar.

Animals↗

Local changes in cerebral glucose utilization during ketamine anesthesia.

Ketamine produces both excitatory and depressant actions in the brain, but there have been conflicting results regarding which structures are affected and the magnitude of the alteration in cerebral metabolism produced. The authors applied the 2-[14C]deoxyglucose method quantitatively to a study of ketamine anesthesia (10 or 30 mg/kg intravenously) in the rat. Ketamine caused both increases and decreases in local cerebral glucose utilization. The areas with altered glucose utilization could be grouped into functional systems. Some structures of the limbic system showed large increases in glucose utilization; indeed the 70 per cent increases in cingulate gyrus and hippocampus were the largest of all regions examined. The extrapyramidal motor system and corpus callosum showed significant but less dramatic (20-40 per cent) increases. On the other hand, decreased metabolism occurred in the somatosensory and auditory systems, with the greatest reduction (40 per cent) in the inferior colliculus. Within some structures, such as the caudate nucleus and visual cortex, a striking redistribution of metabolism which is characterized by a change in the autoradiographic pattern of activity was noted. Reduced glucose utilization in the somatosensory and auditory systems suggests that a selective sensory deprivation occurs during ketamine anesthesia while the increased metabolism in the limbic system is consistent with neurophysiologic studies which have demonstrated seizure activity in this region. Compared with other anesthetics, which tend to produce a generalized decrease in metabolism, the cerebral metabolic effects of ketamine are unique and emphasize that it produces a state of "anesthesia" which is quite different from that of other commonly used drugs.

Anesthesia↗

A new rapid differentiating solubility test for hemoglobin S.

A new test for sickling hemoglobin, SickleQuikTM, has been developed which has definitive advantages over existing turbidity tests. This test utilizes a biphasic liquid reagent system provided in individualized, ready-to-use reaction tubes which are stable at room temperature. The test differentiates homozygous from heterozygous S samples in less than eight minutes. Results are based on the color of a layer formed at the organic-aqueous interface and the color of the lower aqueous phase. Of more than 900 samples tested in independent laboratories, no false positive or false negative results occurred.

Anemia, Sickle Cell↗

Simultaneous immunization with B.C.G., diphtheria-tetanus, and oral poliomyelitis vaccines in children aged 13-14.

The simultaneous administration of B.C.G. vaccine, diphtheria-tetanus toxoid aluminium hydroxide adsorbed vaccine, and oral poliovaccine was studied in 628 children aged 13-14 years between 1966 and 1969 in Newham, London. The efficacy of these vaccines was unaffected by administering them at the same time; routine simultaneous administration is considered justified when organizational difficulties prevent the attainment of high immunization rates with the vaccines given separately. No adverse reactions to B.C.G. or oral poliomyelitis vaccines took place, but 8% of children had moderately severe local reactions after diphtheria-tetanus aluminium hydroxide adsorbed vaccine, which were attributed to diphtheria toxoid.Serological studies showed the need for immunization against diphtheria, tetanus, and poliomyelitis at 13-14 years of age. Because of the adverse reactions to diphtheria toxoid, however, simultaneous administration of tetanus toxoid aluminium hydroxide adsorbed, oral poliomyelitis, and B.C.G. vaccines only is recommended at present.An "adult type" diphtheria-tetanus toxoid might overcome the problem of reactions, though in two to three years' time most children aged 13-14 years will have received diphtheria-tetanus-pertussis vaccine in infancy and reinforcement might then be accomplished by a small intradermal dose of the currently available fluid diphtheria-tetanus vaccine.Continued serological studies of diphtheria and tetanus antitoxins and polio antibody are necessary to determine the future need for reinforcement of immunity; such studies should become an essential part of the surveillance of the community immunization programme.

Adolescent↗