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Biomedical subjects

L Sokoloff

Publications and source records attributed to L Sokoloff.

At least 199 records · Page 11Linked to original sources
PubMed1982

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↗
PubMed1982

Local cerebral glucose utilization in hypothermic and hyperthermic rats.

Local rates of glucose utilization in 38 regions of the CNS were measured in conscious, lightly restrained rats during normothermia (rectal temperature, 37.4 +/- 0.1 degrees C, hypothermia (31.8 +/- 0.1 degrees C), and hyperthermia (40.2 +/- 0.3 degrees C). In 34 of the 38 regions examined (the four exceptions being primary auditory nuclei in the lower brainstem), a significant relationship could be demonstrated between the rate of glucose utilization and body temperature. The magnitude of temperature-related alterations in glucose use displayed considerable regional heterogeneity. In hypothermic rats the reductions in glucose use were proportionately most marked (reduced 35-50% from normothermic) in thalamic nuclei, extrapyramidal and motor areas, septohippocampal formation, and some areas of neocortex and white matter; they were least pronounced in anterior hypothalamus (reduced by 13%), habenula (by 16%), and amygdala (by 22%). In hyperthermic rats, significantly increased glucose utilization was observed in only 16 of the 38 areas examined (e.g., hypothalamus, hippocampus, extrapyramidal system, and raphe nucleus), whereas in a number of major areas (such as the neocortex and thalamus) glucose use was minimally altered with hyperthermia. The regional heterogeneity in the alterations in glucose utilization suggests that caution must be exercised in the interpretation of autoradiographic 2-deoxyglucose investigations in which body temperature disturbances occur.

Animals↗
PubMed1982

Glucose utilization of cerebral gliomas measured by [18F] fluorodeoxyglucose and positron emission tomography.

Positron emission tomography was used to measure local cerebral glucose utilization by the 1-[18F]fluoro-2-deoxy-D-glucose technique in 23 patients with cerebral gliomas. All 10 high-grade (III and IV) astrocytomas demonstrated a region of high activity with a glucose consumption of 7.4 +/- 3.5 (SD) mg/100 gm per minute. The 13 low-grade (I and II) gliomas had a glucose metabolic rate of 4.0 +/- 1.8 mg/100 gm per minute, with no distinctly visible hot spot. Thus, we found a correlation between rate of glycolysis and malignancy in primary cerebral tumors. Cerebral cortical glucose utilization was often depressed in areas adjacent to or neurally connected to the tumor site, and there was focal irregular delta wave EEG activity in these areas.

Adult↗
PubMed1981

Experimental siderosis of articular chondrocytes cultured in vitro.

Siderosis of rabbit articular chondrocytes was produced in vitro as a model for the cartilage damage of hemophilic arthropathy. Both FeSO4 0.1-2.5 mM and rabbit hemoglobin (as hemolyzed serum, 14 mg/ml) caused iron storage in cell and organ culture. FeSO4 was far more effective. The fine structure of the siderosomes resulting from both iron sources was comparable to that observed in hemophilic and other forms of hemosiderosis. Particles resembling ferric oxyhydroxide were included in the FeSO4 but not the hemoglobin derived siderin. Iron storage following FeSO4 was enhanced 5-fold by culturing with rabbit rather than fetal calf serum. Despite repeated washing of the cultures and detachment with trypsin, an extracellular pool of Fe3+ persisted in the cell pellets. Cytotoxicity of Fe was manifested by formation of myelin bodies and a dose-dependent reduction of cell number. There was an inverse relationship between cytotoxicity and iron storage following administration of FeSO4 to five other cell types. Ascorbate 40 micrograms/ml stimulated DNA synthesis but had no protective effect against the cytotoxicity of FeSO4. Little erythrophagocytosis was showen by the chondrocytes. Desferrioxamine (0.01--2.5 mM) was markedly toxic for dividing but not for stationary chondrocytes. Administered after iron storage had been induced with FeSO4, 1.0--2.5 mM desferrioxamine removed stainable siderin granules over the course of 4 days.

Animals↗
PubMed1981

Changes in protein synthesis underlying functional plasticity in immature monkey visual system.

Local rates of cerebral protein synthesis were determined in newborn rhesus monkeys subjected to either acute or chronic monocular visual deprivation. Chronic monocular deprivation resulted in decreased rates of protein synthesis in the laminae of the lateral geniculate nuclei innervated by the deprived eye whereas rates of protein synthesis were normal in geniculate laminae innervated by the functioning eye. Acute monocular deprivation produced no differential changes in rates of protein synthesis in any of the geniculate laminae.

Animals↗
PubMed1981

The extraneural distribution of gamma-hydroxybutyrate.

gamma-Hydroxybutyrate has been found to be widely distributed in both neural and extraneural tissues in the rat. The kidney and brown fat have more than 10 times higher concentrations of gamma-hydroxybutyrate than does the brain. This observation suggests that gamma-hydroxybutyrate may participate in the metabolism of many organs, and that GABA may not be the precursor in extraneural tissues.

3-Hydroxybutyric Acid↗
PubMed1981

Local cerebral glucose utilization and blood flow during metabolic acidosis.

The relationship between local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF) was studied in two groups of normal conscious rats. LCGU was measured by the [14C]deoxyglucose technique and LCBF by the [14C]iodoantipyrine technique. When the LCGU of 39 brain structures was correlated with their respective values of LCBF an excellent correlation (r = 0.96) was obtained between LCGU and LCBF, demonstrating a tight coupling at a local level. Chronic metabolic acidosis was induced in two other groups of rats by adding 0.35 M NH4Cl to the drinking water for 5-6 days. This resulted in a significant (P less than 0.01) reduction in overall cerebral glucose utilization (-29%) and a nonsignificant reduction in overall cerebral blood flow (-8%). This dissociation between the overall cerebral glucose utilization and blood flow during metabolic acidosis cannot be taken as an indicator of uncoupling because the values for LCGU were still well correlated (r = 0.95) with the values for LCBF, indicating a resetting of the coupling mechanism to a new level.

Acidosis↗
PubMed1981

Comparative rates of local cerebral glucose utilization in the visual system of conscious albino and pigmented rats.

We measured local cerebral glucose utilization by means of the [14C]deoxyglucose technique in normal, conscious albino Sprague-Dawley and pigmented Norway rats in the ambient light of the laboratory. There were no differences between the two strains in any structures except those of the visual system. The rates of glucose utilization in all components of the visual system were lower in the albino than in the pigmented rats. The affected structures and percent differences were as follows: visual cortex (17%); stratum griseum superficialis (28%), stratum opticum (17%), and stratum lemnisci (10%) of the superior colliculus; dorsal nucleus (34%) and ventral nucleus (33%) of the lateral geniculate body; and posterolateral thalamus (10%). All differences were statistically significant (p < 0.05) except those in the striatum lemnisci and posterolateral thalamus. These results indicate that the known aberrant neurophysiologic function of the visual system of the albino rats is paralleled by alterations in metabolic activity of its component structures.

Albinism↗
PubMed1981

In vitro culture of rabbit growth plate chondrocytes. 1. Age-dependence of response to fibroblast growth factor and "chondrocyte growth factor".

The growth-promoting effects of pituitary fibroblast growth factor (FGF) and "chondrocyte growth factor" (CGF), a contaminant of NIH-bovine TSH and ovine LH, were studied in monolayer and/or organ culture of epiphyseal plate chondrocytes of rabbits 1 day to 10 weeks old. The response to FGF (50 ng/ml) and CGF(TSH) and CGF(LH) (64 micrograms/ml) was age-dependent. In cultures from animals aged 4 weeks or older, the growth factors consistently stimulated DNA synthesis while decreasing incorporation of radiosulfate into matrix macromolecules. In organ cultures of the growth plate of rabbits less than 1 week old, FGF and NIH-TSH and LH actually diminished rather than promoted incorporation of 3H-thymidine. In organ culture the generation times of newborn rabbit proliferating zone chondrocytes, measured in vivo and in vitro by nuclear grain count dilution in 3H-thymidine autoradiographys, were 11 and 16 to 17 hours respectively. FGF and LH increased the generation time of 1- and 4-day old rabbit chondrocytes from 16 to over 24 hours. The stimulatory effect of CGF(TSH) in the older age group was much greater than that of NIH(LH). The dog-dose response curves of FGF and CGF(LH) were parallel, supporting Jones and Addison's view that the CGF activity of CGF(LH) derives from its content of FGF.

Aging↗
PubMed1981

In vitro culture of rabbit growth plate chondrocytes. 2. Chondrodystrophic mutants.

The epiphyseal plates of newborn normal (Cd/?), dwarf (Dw/Dw) and achondroplastic (ac/ac) rabbits were grown in organ culture for 48 hours. The 3H-thymidine labeling index of proliferating zone chondrocytes from both mutants was below that of normals. The generation time of Dw/Dw animals was longer than that of normals (greater than 24 vs. 17 hours respectively). Inasmuch as the medium was supplemented with 10% fetal calf serum, which presumably contains somatomedin, these data suggest that the Dw/Dw mutant cannot be considered simply a model for pituitary dwarfism. Pituitary fibroblast growth factor (FGF), 50ng/ml, decreased the labeling index of chondrocytes from both Dw/Dw and ac/ac animals. Thus neither a lack of FGF nor an end-organ non-responsiveness to this factor seems to play a role in the pathogenesis of either growth disturbance.

Achondroplasia↗
PubMed1981

Relationships among local functional activity, energy metabolism, and blood flow in the central nervous system.

The results of studies with the [14C]deoxyglucose technique establish that local energy metabolism in cerebral tissues is, as in other tissues, closely coupled to local functional activity. Stimulation of local functional activity increases the local rate of glucose utilization; reduced functional activity depresses it. Local cerebral blood flow is normally distributed among the cerebral structures in almost exact proportion to their rates of glucose utilization and changes together with local glucose consumption in response to altered local functional activity. These results demonstrate that the level of functional activity in the structural and functional components of the central nervous system regulates the local rate of energy metabolism, and local blood flow is adjusted to the local metabolic demand.

Animals↗
PubMed1981

The deoxyglucose method: theory and practice.

By analysis of a kinetic model of the behavior of 2-deoxyglucose and glucose in brain, an operational equation has been derived that allows the computation of the rates of glucose utilization simultaneously in all structures of the central nervous system on the basis of readily measurable variables. Localization in the central nervous system is achieved by a quantitative autoradiographic technique that provides direct visualization of the relative rates of glucose utilization in all parts of the central nervous system.

Animals↗