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Biomedical subjects

L Sokoloff

Publications and source records attributed to L Sokoloff.

At least 181 records · Page 10Linked to original sources
PubMed1983

Comparative effects of acute and chronic administration of amphetamine on local cerebral glucose utilization in the conscious rat.

The 2-deoxyglucose method was employed in rats following either acute or chronic administration of d-amphetamine. The drug was given either by a single intravenous and/or repeated daily intraperitoneal injections or by osmotic pumps implanted subcutaneously. Each mode of administration resulted in a specific constellation of metabolic effects. Acute doses of d-amphetamine, 5 mg/kg, stimulated glucose utilization in a number of cerebral structures, particularly the components of the extrapyramidal motor system. No effects were observed in components of the mesolimbic dopaminergic system. Repeated daily doses of 5 mg/kg for 2 weeks had no effects unless the dosage was progressively increased to toxic levels of 15 mg/kg over a 3-week period. Dosage sustained by osmotic pumps (12-15 mg/kg/day for 1 week or 6-7 mg/kg/day for 2 weeks), however, resulted in a selected increase in glucose utilization in the nucleus accumbens, an important component of the mesolimbic system. This finding may be of significance to the mechanism of amphetamine psychosis, which is sometimes regarded as a model of schizophrenia and is considered to be evidence in support of the dopamine hypothesis of the disease.

Animals↗
PubMed1983

Metabolic mapping in the sympathetic ganglia and brain of the spontaneously hypertensive rat.

Local rates of glucose utilization in the superior cervical, cardiac, and coeliac ganglia were measured by means of the autoradiographic 2-deoxy-D-[14C]glucose method in male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY), 32-34, 46-48, and 78-87 days old. Brain glucose utilization was examined in 78-87-day-old SHR and WKY. At 32-34 days (at which time mean arterial blood pressure was normal and similar in both groups of rats), the rates of glucose utilization of all three sympathetic ganglia were the same in both groups. At 46-48 days, despite the fact that blood pressure had risen significantly in SHR (mean +/- SEM, 136 +/- 3 mm Hg, n = 5, compared to 113 +/- 3 mm Hg, n = 5, in the control WKY), glucose utilization was decreased in the cardiac and coeliac ganglia but not in the superior cervical ganglia of the SHR. At 78-87 days, glucose utilization was reduced in all the sympathetic ganglia of the hypertensive rats. These results suggest that the sympathetic system is less active in SHR and indicate that hyperactivity of the sympathetic nervous system is not part of the mechanism of the hypertension. Of 44 structures examined in the central nervous system, only the external cuneate, vestibular, and fastigial nuclei of the SHR exhibited increased rates of glucose utilization, and no changes were found in any of the other structures. These increases are probably not related to the origin or maintenance of the hypertension, inasmuch as lesioning of the vestibular or fastigial nuclei did not decrease blood pressure in the SHR.

Animals↗
PubMed1983

Frequency-dependent activation of glucose utilization in the superior cervical ganglion by electrical stimulation of cervical sympathetic trunk.

Electrical stimulation of the distal stump of the transected cervical sympathetic trunk produces a frequency-dependent activation of glucose utilization, measured by the deoxy[14C]glucose method, in the superior cervical ganglion of the urethane-anesthetized rat. The frequency dependence falls between 0-15 Hz; at 20 Hz the activation of glucose utilization is no greater than at 15 Hz. Deafferentation of the superior cervical ganglion is transection of the cervical sympathetic trunk does not diminish the rate of glucose utilization in the ganglion in the urethane-anesthetized rat. These results indicate that the rate of energy metabolism in an innervated neural structure is, at least in part, regulated by the impulse frequency of the electrical input to the structure, and this regulation may be an essential component of the mechanism of the coupling of metabolic activity to functional activity in the nervous system.

Animals↗
PubMed1983

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↗
PubMed1983

Factors controlling growth and differentiation in the repair of articular cartilage.

Two avenues of repair of joint cartilage are permissible biologically: 1) replication of chondrocytes, and 2) callus-like metaplasia of articular mesenchyme. The bulk of cartilage present in advanced osteoarthritis (OA) is formed by the latter means. The osteophytes, eburnation, and myxoid proliferation in the pseudocysts of OA should be regarded as reparative phenomena. OA represents more an aberration than an inability of the joint surface to repair.

Animals↗
PubMed1982

The distribution of alterations in energy metabolism in the rat brain produced by apomorphine.

The effects of the putative dopaminergic agonist, apomorphine (0.15-5 mg/kg, i.v.), on glucose utilization in 43 anatomically discrete regions of the rat brain have been examined by the quantitative autoradiographic 2-deoxyglucose technique. Apomorphine failed to alter the rates of glucose utilization in 25 of these regions (for example, primary auditory areas, regions of white matter, hippocampal areas, nucleus accumbens and caudal regions of the neocortex). Dose-dependent alterations in glucose utilization were observed following apomorphine administration in a number of regions known to contain dopaminergic receptors (viz: caudate nucleus, substantia nigra, amygdala, subthalamic nucleus and anterior cingulate cortex). Moreover, dose-dependent alterations in glucose utilization were produced by apomorphine in a number of regions thought to contain few specific dopaminergic receptors (e.g., cerebellar hemisphere and vermis, lamina VI of rostral neocortical areas, and ventral nucleus of the thalamus). The distribution of alterations in glucose utilization following apomorphine administration are considered to reflect the functional involvement of the region in the overall response to apomorphine, and not simply the topography of dopaminergic receptor mechanisms.

Animals↗
PubMed1982

Distribution of effects of haloperidol on energy metabolism in the rat brain.

The effects of the putative dopaminergic antagonist, haloperidol (0.01-10 mg/kg, i.v.), on cerebral glucose utilization in 43 anatomically discrete regions of the rat brain have been examined by the quantitative autoradiographic 2-deoxyglucose technique. Dose-dependent reductions in glucose utilization were observed in 10 regions of the CNS (e.g. hippocampus, ventral thalamus and almost the entire neocortex, with the notable exception of anterior cingulate cortex). Two regions of the CNS (nucleus accumbens and pars compacta of the substantia nigra) displayed dose-related increases in glucose utilization following haloperidol administration. In addition to these specific alterations, the largest doses of haloperidol produced widespread, moderate (about 25%) reductions in glucose utilization throughout the CNS. The prior administration of haloperidol (0.1 mg/kg) prevented the effects on glucose utilization of the administration of apomorphine (1.5 mg/kg) in all regions of the CNS examined. The distribution of alterations in glucose utilization following haloperidol administration are considered in relation to the overall functional consequences of dopaminergic receptor blockade.

Animals↗
PubMed1982

Th central noradrenergic system in the rat: metabolic mapping with alpha-adrenergic blocking agents.

Rates of cerebral glucose utilization were measured by means of the autoradiographic 2-deoxy-D-[14C]glucose technique in 73 normal, awake rats treated with different doses of the alpha-adrenergic blockers, phenoxybenzamine, phentolamine and yohimbine. Three types of responses were elicited by the administration of these drugs. The predominant effect observed after administration of all alpha-blockers was a widespread depression of glucose utilization, particularly within the neocortex. The effect was most pronounced with phenoxybenzamine. In a few structures (locus coeruleus, interstitial nucleus of the stria terminalis, medial forebrain bundle, periventricular nucleus and some medullary and hypothalamic nuclei associated with the regulation of blood pressure) marked increases in glucose utilization were observed. Administration of phentolamine resulted in increased glucose utilization in all the central components of the auditory system (cochlear n., superior olivary n., n. lateral lemniscus, inferior colliculus, medial geniculate body and auditory cortex). Phenoxybenzamine and yohimbine tended to decrease glucose utilization in the auditory system. Alternating columns with higher and lower rates of local glucose consumption were observed in most of the neocortical areas and in the cerebellar vermis. The significance of these columns is not clear.

Adrenergic alpha-Antagonists↗
PubMed1982

Influence of alpha-receptor blocking agents upon metabolic activity in nuclei involved in central control of blood pressure.

The energy metabolism of the central nervous structures involved in the regulation of blood pressure was examined by means of the autoradiographic 2-deoxy-D-[14C]glucose method in normal, awake rats during hypotension induced by the alpha-adrenergic blockers, phentolamine, phenoxybenzamine, and yohimbine. Administration of these alpha-blockers produced a dose-dependent increase of glucose consumption in the medial nucleus of the solitary tract (NTSm), the dorsal motor nucleus of the vagus (DMX), the nucleus ambiguus (NA), and the paraventricular (PAVH) and supraoptic (SO) hypothalamic nuclei. However, in the external cuneate nucleus and in the paramedian reticular nucleus there was a decrease in glucose utilization. These changes appear to be at least partly due to the hypotension produced by the drugs in addition to their central effects; when the hypotension was prevented by administration of the plasma expander, dextran, in phenoxybenzamine-treated rats, the effects were less than those observed in animals with hypotension not limited by dextran infusion.

Adrenergic alpha-Antagonists↗
PubMed1982

Cerebral glucography with positron tomography. Use in normal subjects and in patients with schizophrenia.

Local cerebral uptake of deoxyglucose labeled with fluorine 18 was measured by positron-emission tomography in eight patients with schizophrenia who were not receiving medication and in six age-matched normal volunteers. Subjects sat in an acoustically treated, darkened room with eyes closed after injection of 3 to 5 mCi of deoxyglucose 18F. After uptake, seven to eight horizontal brain scans parallel to the canthomeatal line were done. Scans were treated digitally, with a 2.3-cm strip peeled off each slice and ratios to whole-slice activity computed. Patients with schizophrenia showed lower ratios in the frontal cortex, indicating relatively lower glucose use than normal control subjects; this was consistent with previously reported studies of regional cerebral blood flow. Patients also showed diminished ratios for a 2.3-cm square that was positioned over central gray-matter areas on the left but not on the right side. These findings are preliminary; issues of control of mental activity, brain structure identification, and biologic and anatomic heterogeneity of schizophrenia remain to be explored.

Adolescent↗
PubMed1982

Local cerebral glucose metabolism in newborn dogs: effects of hypoxia and halothane anesthesia.

Local cerebral glucose utilization (LCGU) was measured in 36 neuroanatomical structures of normal awake, halothane-anesthetized, and hypoxic newborn puppies by the autoradiographic 2-[14C]deoxyglucose method. In normal animals, LCGU was highest in the vestibular nucleus and in other gray matter nuclei of the brainstem and declined in a caudal-to-rostral progression through the neuraxis (i.e., LCGU of cerebellum greater than thalamus approximately equal to caudate-putamen greater than cerebral cortex). Lowest rates of glucose metabolism were detected in white matter structures. Halothane anesthesia (1.5% inspired) caused few changes in local glucose metabolism, the most notable being decreased LCGU among structures of the auditory system (cochlear nucleus, lateral lemniscus, inferior colliculus) and increased LCGU in the interpeduncular nucleus. Acute systemic hypoxia (arterial oxygen tension of approximately 12 mm Hg) produced markedly heterogeneous effects on local glucose metabolism: LCGU was increased in some gray matter structures, decreased in the thalamus, and substantially increased in the subcortical white matter and corpus callosum. In puppies whose brains were frozen in situ after 55 minutes of hypoxia, the concentration of lactate was increased ten- to elevenfold in cortical gray and subcortical white matter, but the concentrations of glucose, adenosine triphosphate, and phosphocreatine declined to a greater extent in the white matter. The results suggest that during hypoxia the high rate of glycolysis in white matter exceeded substrate supply so that glucose availability became the limiting factor for local energy production. Such a mechanism may contribute to the white matter injury that often develops following hypoxic-ischemic insults in the perinatal period.

Anesthesia, General↗
PubMed1982

Stimulation of DNA synthesis by ascorbate in cultures of articular chondrocytes.

The addition of 0.2 mM Na L-ascorbate increased the incorporation of 3H-thymidine by rabbit articular chondrocytes in cell and organ culture. The stimulatory response of explants to ascorbate was potentiated by pretreatment of the cartilage with 0.2% clostridial collagenase (type 1) or trypsin for 15-30 minutes. In explants there was a latent period of 3 to 4 days before increased labeling of the nuclei could be detected. The effect was transient and declined after 8 days of culture. It was more evident in organ cultures of immature (3-month-old) than 2- to 3-year-old rabbits. Age differences were not detected in cell cultures. Explants of adult human articular cartilage were stimulated by ascorbate when the medium was supplemented with 10% fresh human serum but not by fetal bovine serum. The findings indicated that synthesis of DNA by articular chondrocytes in situ is regulated by responsiveness of the cells proper to compounds such as vitamin C, by properties of the extracellular matrix, and by factors in the serum. Ascorbate was cytotoxic at concentrations greater than 0.2 mM in the presence of certain batches of serum.

Animals↗
PubMed1982

Effect of purified growth factors on rabbit articular chondrocytes in monolayer culture. I. Dna synthesis.

The ability of purified growth factors, insulin, ascorbate, and several other compounds to stimulate DNA synthesis by rabbit articular chondrocytes was studied in monolayer culture. Platelet-derived growth factor (1 U/ml), pituitary fibroblast growth factor (1-100 ng/ml), and epidermal growth factor (1-50 ng/ml) were stimulatory in a basal medium supplemented with 1% heat-inactivated fetal bovine serum. Insulin, 1-50 micrograms/ml, has small growth-promoting effects but acted synergistically with platelet-derived, pituitary fibroblast, and epidermal growth factors. Increasing concentrations of serum up to 10% enhanced the growth-promoting action of the purified factors, but not of insulin. There were indications of cooperation between insulin and bovine serum albumin and dexamethasone. Ascorbate (0.2 mM) reduced or had little growth-promoting action in the basal medium. At 5 and 10% serum concentrations, however, ascorbate promoted DNA synthesis as effectively as the purified growth factors. No significant stimulatory effect was shown by transferrin, thrombin, L-glutamine, putrescine, selenous acid, dexamethasone, 7S nerve growth factor, or multiplication-stimulating activity.

Animals↗
PubMed1982

Effect of purified growth factors on rabbit articular chondrocytes in monolayer culture. II. Sulfated proteoglycan synthesis.

The effect of 3 purified peptide growth factors--platelet-derived growth factor (PDGF), epidermal growth factor (EGF), pituitary fibroblast growth factor (FGF)--heat-inactivated fetal bovine serum (FBS), insulin, and 0.2 mM ascorbate on synthesis of sulfated proteoglycan by rabbit articular chondrocytes was studied in monolayer culture. Growth of the cells increased linearly as the concentration of heat-inactivated FBS rose from 0 to 30%. Glycosaminoglycan (GAG) synthesis (35SO4/micrograms DNA) was enhanced as the concentration of heat-inactivated FBS went from 0 to 5%. At higher levels of serum, radiosulfate incorporation declined progressively. Two modes of study of the test factors were used: 1) the dose of the factor was increased while the serum concentration was fixed at a low basal level (1% heat-inactivated FBS); 2) the dose of the test factor was kept constant but the level of heat-inactivated FBS varied from 0 to 10%. There was an inverse relationship between GAG and DNA synthesis when proliferation of cells was increased by EGF and platelet lysate. PDGF (1 U/ml) stimulated radiosulfate incorporation as well as DNA formation in the serum-free medium; the values for GAG synthesis did not increase as the serum concentration increased, but the cell mass did. The action of FGF was intermediate between that of EGF and PDGF: with 50 ng FGF/ml, increasing concentrations of serum caused a large progressive reduction of radiosulfate incorporation as growth was stimulated. In basal medium, however, FGF caused mild enhancement of GAG synthesis. Insulin increased aggregatable proteoglycan production far out of proportion to its growth-promoting activity in the presence of 1% heat-inactivated FBS. The response was effaced when higher concentrations of serum were employed. Ascorbate had a unique anabolic effect, increasing both cell growth and proteoglycan synthesis that is not suppressed by higher concentrations of serum. The content of serum and its several peptide and hormonal components thus have divergent effects on growth and proteoglycan synthesis in cell culture. This phenomenon must be taken into account in studying biochemical processes and pharmacologic reactions of articular chondrocytes in vitro.

Animals↗