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Biomedical subjects

D Song

Publications and source records attributed to D Song.

At least 19 recordsLinked to original sources
PubMed2000

Differential potentiative effects of glutamate receptor antagonists in the production of antinociception induced by opioids administered intrathecally in the mouse.

The effect of (+/-)-5-methyl-10,11-dihydro-5H-dibenzo(a,d) cyclohepten-5, 10-imine maleate (MK-801) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) injected intrathecally (i.t.) on the inhibition of the tail-flick response induced by morphine, D-Ala(2)-NmePhe(4)-Gly-ol-enkephalin (DAMGO), beta-endorphin, D-Pen(2,5)-enkephalin (DPDPE), or ¿(trans-3, 4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl] benzeocetamide)¿ (U50, 488H) administered i.t. was studied in ICR mice. The i.t. injection of MK-801 (2 microg) or CNQX (1 microg) alone did not affect the basal tail-flick response. Morphine (0.2 microg), DAMGO (0.8 ng), beta-endorphin (0.1 microg), DPDPE (0.5 microg) or U50, 488H (6 microg) caused only slight inhibition of the tail-flick response. CNQX injected i.t., but not MK-801, enhanced the inhibition of the tail-flick response induced by i.t. administered morphine, DAMGO, DPDPE or U50, 488H. However, CNQX or MK-801 injected i.t. was not effective in enhancing the inhibition of the tail-flick response induced by beta-endorphin administered i.t. The potentiating effect of CNQX on tail-flick inhibition induced by morphine, DAMGO, DPDPE or U50, 488H was blocked by naloxone (from 1 to 20 microg), yohimbine (from 1 to 20 microg) or methysergide (from 1 to 20 microg) injected i.t. in a dose-dependent manner. Our results suggest that the blockade of AMPA/kainate receptors located in the spinal cord appears to be involved in enhancing the inhibition of the tail-flick response induced by stimulation of spinal mu-, delta-, and kappa-opioid receptors. Furthermore, this potentiating action may be mediated by spinal noradrenergic and serotonergic receptors. However, N-methyl-D-aspartate receptors may not be involved in modulating the inhibition of the tail-flick response induced by various opioids administered spinally.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2000

Effects of the anion channel blocker DIDS on ouabain- and high K(+)-induced release of amino acids from the rat cerebral cortex.

Amino acid release from the rat cerebral cortex was analyzed using an in vivo cortical cup perfusion model. Topical applications of ouabain or high extracellular K(+) were used to mimic two dimensions of ischemic conditions which promote cell swelling and amino acid release. Ouabain (30 microM) induced significant releases of taurine, gamma-aminobutyric acid (GABA), aspartate, glutamate and phosphoethanolamine. The anion channel blocker, 4, 4'-diisothiocyanatostilbene-2, 2'-disulfonic acid (DIDS; 1 mM), inhibited ouabain-induced release of all these amino acids except for glutamate. Exposure to high extracellular K(+) (75 mM) induced a delayed rise in the levels of taurine in the superfusates and an immediate increase in GABA levels. There were no significant releases of other amino acids. The release of taurine and GABA was sensitive to the blocking of anion channels with DIDS. Both ouabain- and high K(+)-induced taurine release is likely to be mediated by DIDS sensitive anion channels. The extracellular accumulation of the other amino acids, where insensitive to DIDS, may be mediated by mechanisms other than swelling-induced anion channels.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2000

Effects of Cosolvents and pH on Protein Adsorption on Polystyrene Latex: A Dynamic Light Scattering Study.

Dynamic light scattering was used to study the adsorption of two proteins with different surface properties (IgG and HSA) on negatively charged polystyrene latex. The proteins were adsorbed from water and from water/methanol and water/glycerol mixtures at various pH. Some striking differences between the adsorption behaviors of the proteins were observed. Whereas the thickness of the adsorbed layer of HSA was extremely sensitive to pH and solvent composition, that of IgG was not. IgG mainly showed an end-on orientation on polystyrene whereas several different surface orientations are suggested for HSA under different conditions. The addition of methanol inhibited the adsorption of HSA on the latex, but it did not affect the adsorption of IgG. In contrast, the addition of glycerol increased the thickness of the adsorbed layers of both proteins. So, the orientation of IgG on the latex is insensitive to pH but is a function of the kind of solvent whereas both pH and solvent strongly affect the adsorption of HSA. This is a puzzling result since both cosolvents should equally affect the adsorption of both proteins if the dominant forces for adsorption are the same. Therefore, we concluded that, whereas hydrophobic interactions are the dominant force in the adsorption behavior of HSA, van der Waals forces are the main forces involved in the attachment of IgG to the lattices. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Mechanisms involved in coronary artery dilatation during respiratory acidosis in the isolated perfused rat heart.

A rat Langendorff heart preparation, perfused at constant pressure, was used to evaluate the role of K(ATP) channels in respiratory acidosis-induced coronary hyperemia. Prior administration of glibenclamide, an inhibitor of K(ATP) channels, reduced basal flow rates and eliminated the hyperemia associated with hypercapnia. These results implicate K(ATP) channels as a functional link in the respiratory acidosis-induced increase in coronary flow.

Acidosis, Respiratory↗
PubMed2000

Topical insulin and accumulation of excitotoxic and other amino acids in ischemic rat cerebral cortex.

Insulin plays a neuroprotectant role in the brain and spinal cord during ischemia. However, studies have shown insulin to increase the sensitivity of cultured cortical cells to glutamate toxicity. The present study looked at the relationship between topically administered insulin (1 mIU insulin/ml and 100 mIU insulin/ml) during a four-vessel model of global ischemia and the accumulation of amino acids, especially glutamate, from the ischemic rat cerebral cortex. The lower dose of insulin was found to attenuate the release of excitotoxic and other amino acids from the cortex in ischemia/reperfusion. This may occur because insulin increases glucose availability to glial cells resulting in maintenance of glycolysis and ionic pumps that can reduce glutamate release and maintain uptake during ischemia/reperfusion. The higher dose of insulin, which significantly increased the amount of aspartate, glutamate, taurine, and GABA during reperfusion, may act to stimulate the amount of glycogen stored in astrocytes, reducing the availability of glucose for metabolic purposes.

Administration, Topical↗
PubMed2000

Topical glucose and accumulation of excitotoxic and other amino acids in ischemic cerebral cortex.

Pre-ischemic hyperglycemia aggravates brain damage due to transient global ischemia as demonstrated by exacerbation of brain lesions. Lactacidosis and elevated glutamate levels have been implicated as mechanisms of the increased damage. Our objective was to determine the effects of different levels of glucose (0, 66.5, 450 mg/dL) in cortical superfusates on the ischemia/reperfusion-evoked release of amino acids from the rat cerebral cortex. Physiologic levels of glucose significantly reduced the amount of aspartate, glutamate and gamma-aminobutyric acid and the supra-physiologic levels of glucose reduced the amount of aspartate and phosphoethanolamine released from the cortex during ischemia/reperfusion in comparison with no glucose. The decrease in glutamate release may be due to increased availability of glucose for glycolysis with the subsequent formation of ATP and lactate, which has been shown to act as an energy source for neurons. The decreased levels may also reflect the continued energy-dependent uptake of glutamate by glial cells.

Animals↗
PubMed1999

Melittin enhances amino acid and free fatty acid release from the in vivo cerebral cortex.

The effects of the phospholipase activator melittin on amino acid and free fatty acid release from the rat cerebral cortex were monitored and compared with those of a secretory PLA(2), using a cortical cup technique with topical application of these agents in artificial cerebrospinal fluid. Melittin (10 microg/ml; 3.5 microM) elicited a rapid increase in the levels of superfusate amino acids; aspartate, glutamate, GABA, glycine, taurine, glutamine, phosphoethanolamine, alanine, serine and the free fatty acids arachidonic, linoleic, palmitic and oleic acid. PLA(2) (25 microg/ml) also enhanced amino acid efflux but its effects were significantly slower to develop than those of melittin. The results confirm previous indications of an ability of phospholipases to augment extracellular levels of several amino acids, including the excitotoxins glutamate and aspartate, and further implicate phospholipase activation as a significant contributor to cerebral ischemic injury. Melittin has the potential to be a useful tool with which to evaluate the role of phospholipases in ischemia injury.

Amino Acids↗
PubMed1999

Hyposmotically induced amino acid release from the rat cerebral cortex: role of phospholipases and protein kinases.

In an evaluation of the contribution of swelling-induced amino acid release, through the regulatory volume decrease (RVD) process, to cerebral ischemic injury, studies of the role of phospholipases and protein kinases in the response to hyposmotic stress were undertaken using an in vivo rat cortical cup model. Hyposmotic stress induced significant releases of aspartate, glutamate, glycine, phosphoethanolamine, taurine and GABA from the rat cerebral cortex. Taurine release was most affected, exhibiting a greater than 9-fold increase during the hyposmotic stimulus. The phospholipase A2 (PLA2) inhibitors 4-bromophenacyl bromide (1 microM) and 7,7-dimethyleicosadienoic acid (5 microM) had no significant effects on hyposmotically induced amino acid release. AACOCF3 (50 microM), an inhibitor of cytosolic PLA2 decreased taurine release to 84% of DMSO controls. The release of the other amino acids was not affected. The phospholipase C inhibitor U73122 (5 microM) had no significant effects on amino acid release. The protein kinase C (PKC) inhibitor chelerythrine (5 microM) significantly reduced hyposmotically induced taurine release to 72% of saline controls but had no significant effects on the other amino acids. Stimulation of PKC with phorbol 12-myristate, 13-acetate (10 microM) did not significantly change taurine, glutamate, glycine or phosphethanolamine release. The releases of aspartate and GABA were enhanced 2 to 3 fold. Phorbol 12,13-didecanoate (10 microM), another potent stimulator of PKC, significantly increased taurine release to 122% of DMSO controls. The releases of aspartate, glutamate and glycine were enhanced 2.5 to 3.5 fold. Similarly, stimulation of protein kinase A with forskolin (100 microM) significantly increased taurine, aspartate, and glycine release 1.5- to 2-fold compared to DMSO controls. In summary, phospholipases may play a minor role in volume regulation. These studies also support the hypothesis that protein kinases play a modulatory role in the RVD response. The results show that although RVD may play a role, additional mechanisms, including phospholipase activation, must be involved in the ischemia-evoked release of excitotoxic amino acids.

Acetophenones↗
PubMed1999

Failure of kynurenic acid to inhibit amino acid release from the ischemic rat cerebral cortex.

The ability of a broad spectrum glutamatergic receptor antagonist, kynurenic acid (1 and 5 mM) to attenuate release of excitant and other amino acids from the ischemic cerebral cortex was examined in a four vessel occlusion rat model. Kynurenic acid, administered topically onto the cortex in artificial cerebrospinal fluid using bilateral cortical cups, failed to attenuate ischemia-evoked release of aspartate, glutamate, phosphoethanolamine, taurine and at 1 (but not 5) mM it depressed GABA release. There was no effect on basal, pre-ischemic, release. This result suggests that ischemia-evoked amino acid release is not a significant consequence of the activation of ionotropic receptors by synaptically released glutamate.

Amino Acids↗
PubMed1999

Lactate reduces amino acid release and fuels recovery of function in the ischemic brain.

Pre-ischemic hyperglycemia exacerbates the neuronal injury associated with cerebral ischemia/reperfusion, possibly because the accumulation of glycolytically derived lactate causes acidosis. Twenty minutes of four vessel occlusion caused significant increases in rat cerebral cortical superfusate levels of aspartate, glutamate, phosphoethanolamine, taurine, and GABA. Lactate (20 mM), applied topically, significantly reduced the ischemia/reperfusion evoked releases of glutamate and GABA, with further reductions following the higher dose (40 mM), which also significantly reduced the evoked release(s) of the other amino acids. EEG recovery was robust in the presence of 40 mM lactate. These results substantiate the ability of lactate to serve as a neuronal energy substrate but question the role of lactate accumulation in the enhancement of ischemic brain injury by hyperglycemia.

Amino Acids↗
PubMed1999

Effect of hyperglycemia on extracellular levels of amino acids and free fatty acids in the ischemic/reperfused rat cerebral cortex.

This study analyzed the effects of pre-existing hyperglycemia on the extracellular levels of glutamate, other amino acids and free fatty acids, including arachidonic acid, in the ischemic/reperfused rat cerebral cortex, using a cortical cup technique. Forebrain cerebral ischemia (20 min) was induced by four vessel occlusion. Glucose (3.4 g/kg) was administered 30 min prior to ischemia. Glucose administration had no effect on basal levels of superfusate amino acids and reduced basal levels of linoleic and oleic acids. Cerebral ischemia elicited increased superfusate levels of aspartate, glutamate, phosphoethanolamine, taurine, gamma-aminobutyric acid (GABA) and arachidonic acid when compared with basal levels. Reperfusion caused a further increase in phosphoethanolamine and arachidonic acid levels and transient increases in linoleic, oleic and palmitic acids. Hyperglycemia resulted in significantly reduced levels of glutamate, phosphoethanolamine, GABA and arachidonic, myristic, palmitic, linoleic and oleic acids during ischemia/reperfusion in comparison with the saline-injected ischemic controls. The results indicate that ischemia/reperfusion-evoked increases in the extracellular levels of glutamate, certain other amino acids and free fatty acids are attenuated by prior systemic glucose administration.

Amino Acids↗
PubMed1999

Application of two-dimensional high-performance liquid chromatography--mass spectrometry with particle beam interface.

The use of a particle beam interface (PBI) in LC-MS has faded because of its poor resolution and low sensitivity for many compounds. It also does not perform well in reversed-phase systems with a high percentage of water. This manuscript describes two-dimensional LC to overcome the problems of PBI, both in the identification of unknown samples and in the quantitative determination of metabolites of vitamin D in human plasma. For the identification of unknown components, the reversed-phase solvent in the first dimension was transferred to an isocratic normal solvent system in second dimension by column switching. Moreover, only the peaks of interest (components) in the first dimension were transferred into the second LC column for mass analysis. For the quantitative determination of the metabolite of vitamin D, the peak width of analyte in the second dimension was greatly narrowed, and interference was excluded such that high sensitivity and resolution resulted. The limit of quantification for the test metabolite of vitamin D in human plasma can reach 0.050 ng/ml with injection volume of 50 microl.

Chromatography, High Pressure Liquid↗
PubMed1999

Prepulse inhibition of startle and the neurobiology of primary nocturnal enuresis.

BACKGROUND: Children with primary nocturnal enuresis (PNE) wet the bed during all stages of sleep and irrespective of state of arousal, suggesting that during sleep, when voluntary, i.e., cortical control, is not available, the signal from the distended bladder is not registered in the subcortical centers inhibiting micturition. Deficient prepulse inhibition (PPI) of startle has been reported in PNE. This study evaluates the association of this PPI deficit in PNE with comorbidity with attention-deficit hyperactivity disorder (ADHD) and with intelligence. METHODS: Prepulse modulation of startle was studied in 96 boys with PNE and 105 nonenuretic boys using intervals of 60, 120, and 4000 msec between the onset of a 75-dB 1000-Hz tone and a 104-dB noise burst. Thirty-one percent of the enuretic and 36% of the nonenuretic boys were diagnosed with ADHD. RESULTS: After adjustment for presence or absence of ADHD, lower or higher IQ, age, and unmodulated startle amplitude, there was a significant association between PNE and deficient PPI of startle following the 120-msec prepulse interval. Those enuretic boys who also were ADHD or had higher performance IQs (> or = 110) showed the greatest PPI deficit. CONCLUSIONS: A common deficiency of inhibitory signal processing in the brain stem may underlie both deficient PPI and the inability to inhibit micturition in PNE. Strong familiarity for PNE, ADHD, and intelligence suggests a possible genetic mediation of these effects.

Acoustic Stimulation↗
PubMed1999

Effects of hyperosmolarity and ion substitutions on amino acid efflux from the ischemic rat cerebral cortex.

The contributions of sodium and chloride ions and of osmotic stresses to the ischemia-evoked efflux of excitotoxic and other amino acids were explored using a rat four vessel occlusion model. Replacement of Na+ with choline or N-methyl-D-glucamine (NMDG) and of Cl- with sulfate or gluconate was used to evaluate the contribution that these ions make to amino acid efflux. The contribution of ischemia-evoked swelling to amino acid release was studied by applying mannitol or sucrose to minimize the cell volume increases and the compensatory regulatory volume decrease evoked efflux of amino acids. Aliquots of artificial cerebrospinal fluid (aCSF), appropriately adjusted for ion replacement or 150 mM mannitol or sucrose, were pipetted into cortical cups 35 min prior to ischemia and perfusate samples were obtained prior to, during and following ischemia (20 min) and reperfusion (40 min). Replacement of Na+ by NMDG depressed basal (normoxic) efflux of most amino acids, with choline substitution having little effect. During ischemia NMDG substitution increased glutamate and GABA efflux and choline enhanced the release of aspartate, glutamate, GABA and taurine. A reduction in extracellular Na+ would facilitate reversal of Na+-dependent transporters with extrusion of amino acids. Another possible explanation for the elevated release is that the absence of Na+ would inhibit the Ca2+/Na+ counter transport system, with a deleterious accumulation of intracellular Ca2+. Chloride replacement with sulfate or gluconate enhanced the efflux of aspartate, glutamate, GABA and taurine during ischemia. Removal of Cl- would depolarize cells, and block the Cl--dependent action of inhibitory amino acid transmitters, with both actions enhancing the ischemic injury and, consequently, amino acid release. Exposure to hyperosmotic mannitol (150 mM) aCSF enhanced ischemia-evoked release of some amino acids (taurine, GABA) and decreased that of aspartate and phosphoethanolamine. Sucrose aCSF enhanced the ischemia-evoked release of most amino acids. A potential explanation for these observations is that both agents may be able to rapidly penetrate the plasma membranes of ischemic neurons, actually contributing to the release of other osmolytes. The unanticipated nature of many of the observations made during these manipulations of the aCSF serves to accentuate the complex nature of the mechanisms responsible for the ischemia-evoked amino acid efflux into the interstitial spaces.

Animals↗
PubMed1999

Regional expression of heat shock protein 72 mRNA following mild and severe hypoxia in neonatal piglet brain.

The present study examined the effect of hypoxia on expression of 72-kDa heat shock protein (hsp72) mRNA in the newborn brain. The studies were carried out in anesthetized and mechanically ventilated newborn piglets, age 3-5 days. Hypoxic insult was induced by decreasing the fraction of inspired oxygen (FiO2) from 21% to 6% or 10% for 1 h. Oxygen pressure in the microvasculature of the cortex (cortical pO2) was measured by oxygen dependent quenching of the phosphorescence of phosphor dissolved in blood. Following the two hours of normoxic recovery, regional expression of the 72-kDa heat shock protein (hsp72) mRNA was determined using in situ hybridization and autoradiography. Two grades of hypoxia were studied. Mild hypoxia (cortical pO2 = 10-30 mm Hg) induced the expression of hsp72 mRNA predominantly in the subcortical white matter. In individual animals of this group, the extent of expression varied from isolated regions to widespread involvement of the white matter. Severe hypoxia (cortical pO2 = 3-10 mm Hg) induced the expression of hsp72 mRNA in both white and gray matter regions, with strong expression occurring in the cerebral cortex of individual animals. The present results indicate that immature white matter is more sensitive than gray matter to the hypoxia induced expression of hsp72 mRNA. Further, increased expression of hsp72 mRNA may be an indicator of a pathologic degree of hypoxic stress, and the observed increase may indicate that in the newborn brain the immature white matter is particularly sensitive to injury by hypoxia-ischemia and reperfusion.

Animals↗
PubMed1999

Increased nitric oxide synthase expression in aorta of cirrhotic rats.

The characteristic cardiovascular changes in liver cirrhosis are vasodilatation and increased cardiac output. Augmented activity of the vasorelaxant factor, nitric oxide (NO), stimulated by cytokines, have been suggested to play a role in the pathogenesis, but previous studies show conflicting results. We therefore aimed to evaluate the entire pathway from cytokines to the final metabolites, nitrate/nitrite. The levels of serum Tumor Necrosis Factor-alpha (TNFalpha) and nitrate/nitrite (NOx) were measured, and aorta content of inducible (iNOS) and endothelial nitric oxide synthase (eNOS) mRNA and protein were determined by reverse-transcription polymerase chain reaction and Western blotting in rats with cirrhosis due to chronic bile duct ligation and sham-operated controls. Compared to control rats, serum TNFalpha levels were significantly elevated in cirrhotic rats (48.4+/-21.1 vs 16.8+/-9.0 pg/ml, p<0.01); iNOS mRNA was detectable whereas it was absent in controls, and eNOS mRNA levels was significantly higher in aortae of cirrhotic rats. Aortic eNOS protein content was significantly higher in cirrhotic rats, but iNOS protein was undetectable by Western blotting in both groups. Serum NOx concentrations in the cirrhotic group were significantly higher than those in controls (3.5+/-1.0 vs 2.3+/-0.5 microM, p<0.01). These results suggest that NO activity in cirrhosis is increased, and is predominantly due to eNOS since the detectable iNOS mRNA does not seem to be expressed as protein. The increased NOS activity in the arterial system may play a role in the systemic hemodynamic changes occurring in cirrhosis.

Animals↗