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D J Stone

Publications and source records attributed to D J Stone.

At least 37 records · Page 2Linked to original sources
PubMed1997

Astrocytes and microglia respond to estrogen with increased apoE mRNA in vivo and in vitro.

This study examined the regulation of apolipoprotein E (apoE) by 17beta-estradiol (E2) in brain glia, using rats with regular ovulatory cycles as an in vivo model and cultured astrocytes and mixed glia as in vitro models. Two brain regions were examined which had demonstrated transient synaptic remodeling during the estrous cycle. In the hippocampal CA1 region and the hypothalamic arcuate nucleus, apoE mRNA was elevated at proestrus when plasma E2 was high and synaptic density was increasing. Both astrocytes and microglia contributed to this increase in apoE mRNA. In vitro, E2 treatment had no effect on apoE mRNA levels in monotypic cultures of either astrocytes or microglia. In contrast, mixed glial cultures responded to E2 with increased apoE mRNA and protein, suggesting that heterotypic cellular interactions are important in the brain response to estrogens. In situ hybridization in combination with cell-specific markers showed that E2 increased apoE mRNA levels in both astrocytes and microglia. These results, which are the first evidence of apoE mRNA localization to microglia in vivo and the control of apoE expression in brain cells by estrogens, are discussed in terms of the possible protective role of E2 in Alzheimer's disease and prior findings that emphasize the expression of apoE mRNA in astrocytes within the brain.

Animals↗
PubMed1997

Efficient designs for studying synergistic drug combinations.

Distinguishing between pharmacologically additive and synergistic drug combinations requires experimental designs and statistical analyses that often require appreciable numbers of animals and much experimenter time. The current study employed a design in which individual dose-effect data from each drug were translated into theoretically additive total dose combinations, in a fixed drug proportion, in order to produce a composite additive dose-effect relation that could be compared with that of an actual mixture having the same proportion. Results from this approach, using a combination of intrathecal doses of morphine and clonidine, were virtually identical to those using isobolographic analysis of the same data set. Both analyses showed significant synergism for this combination and, in each method, it was not necessary to constrain the drug regression lines to parallelism. In contrast to the isobole approach, the use of the composite additive dose-effect relation also allows observation of the interaction over a range of effects while reducing the size of the data sets needed.

Analgesia↗
PubMed1997

Increased transcription of the astrocyte gene GFAP during middle-age is attenuated by food restriction: implications for the role of oxidative stress.

Glial fibrillary acidic protein (GFAP), an intermediate filament of astrocytes, shows increased expression during aging. Because we found that chronic food restriction retards the increase of GFAP mRNA in aging rats and because food restriction decreases the load of oxidized proteins and lipids in association with increased life span, we investigated the regulation of GFAP during oxidative stress and aging. First, we showed that food restriction decreased the transcription of GFAP in aging rats. This result generalizes effects of food restriction on age changes of transcription; whether transcription decreases during aging as in hepatic genes, or increases during aging as in astrocytic GFAP, food restriction attenuates the age change. Moreover, food restriction decreased microglial activation during aging, which suggested the hypothesis that GFAP expression is sensitive to oxidative stress. Because GFAP transcription in cultured glia is increased by oxidative stress in response to hydrogen peroxide and cysteamine whether or not microglia were present, we conclude that responses of GFAP to oxidative stress in astrocytes do not depend on microglial activation. The results implicate oxidative stress in the increased expression of GFAP during aging, but also in responses to brain injury.

Aging↗
PubMed1996

Transcription supports age-related increases of GFAP gene expression in the male rat brain.

During aging, rodent and human brains show progressive increases in the levels of glial fibrillary acidic protein (GFAP) mRNA and protein. The role of transcription was investigated by in situ hybridization, using an intron-containing cRNA probe as a measure of primary GFAP transcripts. We found parallel age-related increases in GFAP intron RNA in the hippocampus, internal capsule, and corpus callosum of 3 versus 24 month old male F344 rats. We conclude that increased transcription supports the age-related increase of GFAP mRNA and protein. GFAP is a unique example of a gene that shows increased expression during aging in contrast to the decreased transcription of certain genes reported in non-neural tissues.

Aging↗
PubMed1996

Airway management in neuroanaesthesia.

PURPOSE: Airway management in neurosurgical patients presents unique challenges to the anaesthetist. This review will consider specific approaches to numerous problems in airway management related to logistical, physiological and anatomical concerns. The goal is to provide a clinically oriented and practical discussion regarding issues of airway management in neurosurgical patients. SOURCE: The recent literature has been reviewed regarding airway management options and related perioperative complications in the neurosurgical population. This is interlaced with approaches to many of the problems and their solutions based on experience gained in a very busy university neurosurgical practice over the past decade. PRINCIPAL FINDINGS: Specific pathophysiological alterations in the neurosurgical patient influence the technique chosen for securing an airway. These relate to the presence of increased intracranial pressure, intracranial aneurysms or arteriovenous malformations. Other important disorders influencing airway management include severe coronary artery disease, acromegaly and congenital airway difficulties. Stereotactic neurosurgery and conscious sedation for various neurosurgical procedures also provide unique challenges. There are other considerations unique to the neurosurgical patient such as intra-and postoperative airway obstruction and the timing of postoperative extubation. CONCLUSION: The demands for airway management in neuroanaesthesia require expertise in the various modes of securing the airway while considering the patient's physiological requirements as well as the unique surgical demands.

Anesthesia↗
PubMed1996

Alpha-subunit G-protein antisense oligodeoxynucleotide effects on supraspinal (i.c.v.) alpha2-adrenoceptor antinociception in mice.

An in vivo antisense strategy was used to examine the involvement of G-protein subunits in supraspinal (intracerebroventricular; i.c.v.) alpha2-adrenoceptor-mediated antinociception. Mice that were injected with 33-mer antisense oligodeoxyribonucleotides (6 nmol) or vehicle were tested (tail-flick) with an agonist (clonidine, guanfacine or BH-T 920) administered i.c.v. 18 - 24 h later. Gi3alpha antisense treatment attenuated BH-T 920 and clonidine-induced antinociception. Gi2alpha antisense produced differential effects on the three agonists. Gi1alpha and G(s)alpha antisense treatment had no significant effect. Together with the previous demonstration that i.c.v. mu-opioid antinociception is mediated via Gi2alpha, the present results suggest that different receptors may mediate antinociception via different G-protein subunits and, hence, that specific subunits might offer novel targets for drug discovery.

Adrenergic alpha-Agonists↗
PubMed1996

Could dual G-protein coupling explain [D-Met2]FMRFamide's mixed action in vivo?

In vitro studies have demonstrated that FMRFamide-related peptide receptors can be coupled to different G-proteins, mediating opposite stimulatory and inhibitory effects. The present study tested whether this duality might extend to effects in vivo. Antinociception in mice of ICV [D-Met2]FMRFamide, which produced agonist [ED50 = 36.3 micrograms (61.6 nmol)] and antagonist [ID50 = 0.72 microgram (1.22 nmol)] actions, was attenuated by 24-h pretreatment with ICV pertussis toxin (ID50 = 0.55 microgram) or cholera toxin (ID50 = 0.09 microgram), suggesting that [D-Met2]FMRFamide in vivo effects might also be explained by dual Gi/Gs, coupling.

Amino Acid Sequence↗
PubMed1992

Emergency management of the airway outside the operating room.

Successful emergency airway intervention incorporates the anaesthetist's basic skills in airway management with the knowledge of the special nature of the clinical problems that arise outside the operating room. While a thorough but rapid evaluation of the key anatomical and physiological factors of an individual patient may result in an obvious choice for optimal management, clinical problems often arise in which there is not an evident "best approach." In these less clear-cut situations, the anaesthetist may do well to employ those techniques with which she/he has the greatest skills and experience. At times, however, some degree of creative improvisation is required to care for an especially difficult problem.

Anesthesiology↗
PubMed1992

Thiopental reduces halothane MAC in rats.

The anesthetic contribution of specific plasma concentrations of thiopental has not been previously defined in laboratory animals. The plasma thiopental concentrations needed to reduce the anesthetic requirement for halothane by fractions of the minimum alveolar anesthetic concentration (MAC) were assessed in the rat. After steady-state thiopental plasma concentrations were established with a constant infusion, the tail-clamp technique was used to determine control MAC and the MAC of halothane with increasing concentrations of thiopental. We observed progressive reductions in halothane MAC. This required logarithmic increases in thiopental concentration rather than linear ones. A nonlinear reduction in anesthetic requirement was noted with an approximate 50% reduction in MAC at a thiopental plasma concentration of 7.4 micrograms/mL and an approximate 90% reduction at 32 micrograms/mL. Thiopental appears to provide essentially complete anesthesia in the rat model with a logarithmic contribution of increasing plasma concentrations.

Animals↗
PubMed1989

Endothelium-dependent effects of halothane, enflurane, and isoflurane on isolated rat aortic vascular rings.

To determine the endothelium-dependent vascular effects of halothane, enflurane, and isoflurane, isometric tension was recorded in isolated ring preparations of rat thoracic aorta suspended in Kreb's buffer and aerated with 95% O2/5% CO2. One set of the rings had intact endothelium and the other set of the rings had the endothelium mechanically denuded. The rings were precontracted with phenylephrine (1 x 10(-6) M). Halothane, enflurane, or isoflurane gas was bubbled through the baths at increasing concentrations (0.5-5.0%) in preparations with and without indomethacin (28 microM). Endothelium-intact rings demonstrated significant (P less than 0.05) vasoconstriction at low concentrations of both isoflurane and enflurane followed by vasodilation at higher concentrations. Halothane also induced vasoconstriction in some rings, but its mean effect was not significantly different from control. After discontinuation of the anesthetic gas, endothelium-intact rings demonstrated a rebound vasoconstriction above previous maximal levels for all three anesthetics. When indomethacin was added to the baths, the vasoconstriction was potentiated and was statistically significant for all three anesthetics. These results suggest that at low concentrations, enflurane and isoflurane cause vasoconstriction through inhibition of basal EDRF production and/or stimulation of the release of an endothelium-derived constricting factor. At higher anesthetic concentrations, a direct vasodilating effect of the anesthetic predominates. The potentiation of vasoconstriction in the presence of indomethacin suggests that these volatile anesthetics stimulate the release of a vasodilating prostanoid from endothelium.

Animals↗
PubMed1988

Hypoploidy and hyperplasia in the developing brain exposed to alcohol in utero.

Prenatal effects of acute maternal alcohol ingestion on chromosome segregation and mitotic frequency in the brain cells of the fetus were evaluated in mice by direct chromosome and mitotic counts and by flow cytometry. Fetuses were exposed to acute transplacental doses of alcohol for 4 days and killed on the fifth day. Those litters in which the fetuses were developed to the equivalent of normal 16th-17th-day gestation age were analyzed. A marked increase in the number of hypoploid metaphases was observed in direct proportion to the dose ingested by the mother. An over 30% increase in hypoploidy over controls was measured in the fetuses exposed to the highest dose. Counts of mitotic cells showed an over tenfold increase in the mitotic index of the fetal brain exposed to alcohol. Flow cytometric measurements of DNA content in isolated fetal brain cell nuclei showed a shift from a single G0/G1 peak in controls to a bimodal G0/G1-G2 + M distribution in alcohol-exposed fetuses of the same developmental age.

Animals↗