Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The concentrations of extracellular glutamate (Glu), aspartate (Asp) and glycine (Gly) were measured by microdialysis method in the cortex and hippocampus before, during and after 15 min of total cerebral ischemia in dogs. The correlations between the concentrations of amino acids and the changes in EEG and evoked potentials (EP) after ischemia were evaluated. Total cerebral ischemia was achieved by occluding the ascending aorta and the caval veins. The concentrations of Glu in the hippocampus significantly increased from 1.73 +/- 0.59 (mean +/- SEM) nmol.ml(-1) at pre-ischemia to 5.46 +/- 1.34 (P < 0.05) during ischemia and 14.37 +/- 3.70 (P < 0.01) 0-15 min after ischemia, and returned to the pre-ischemic level 30 min after ischemia. The concentration of hippocampal Glu 0-15 min after ischemia had significant negative correlations with the EEG-EP scores (0 = serious deterioration of electrical function and 6 = normal electrical function) 30 min, 3 hr and 5 hr after ischemia (r = -0.69, P < 0.05 : r = -0.67, P < 0.05 : r = -0.70, P < 0.05, respectively). The increase of the extracellular Glu concentration in the hippocampus immediately after ischemia may aggravate the neurological outcome after total cerebral ischemia.
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PMID:Elevation of the extracellular glutamate concentration in the hippocampus after total cerebral ischemia related to the deterioration of the recovery in EEG and evoked potentials in dogs. 1527 20

The hypothalamus is a key area for the integration of the autonomic features of affective behavior. Hypothalamic defence area (HDA) stimulation evokes major cardiorespiratory changes as well as modifications of general autonomic activity both in the anesthetized and conscious animal. Micturition is due to an increase in pelvic parasympathetic activity and, in the cat, the anterior hypothalamus has been implicated in urinary bladder control with the demonstration of a dorsolateral vesicoconstrictor pathway and a ventromedial inhibitory pathway. In this study we have investigated the effect of electrical and chemical stimulation of the HDA on bladder pressure and contractions in rat. Female rats (n = 15) were anesthetized, paralyzed and ventilated artificially. Arterial blood pressure, heart rate, urinary bladder pressure and pelvic nerve activity were recorded. HDA was electrically (1 ms, 100 Hz, 5-10 s train at intensities up to 150 micro A) and chemically (sodium glutamate, 50 nl, 2mM) stimulated. For statistical analysis the t-test was used, data were expressed as mean +/- SEM. Values of t were taken as significant when p < 0.05.HDA stimulation at 100-150 micro A evoked changes of both mean blood pressure (mBP) and bladder pressure (BlP). However, stimulation at < 30 micro A allowed a distinction within HDA of two different regions, at the same antero-posterior and lateral level, but separated 100-150 micro m in depth, which evoked differential effects on blood pressure and urinary bladder pressure. Results show that low intensity stimulation at ventral sites evoked a significant increase of mBP (from 102 +/- 5.9 to 127 +/- 8.6 mmHg, n = 10, p < 0.0001) with little changes of BlP (from 12 +/- 2.2 to 16 +/- 2.9 cmH(2)O, n = 10, p < 0.0005), whilst at more dorsal sites significant increases of BlP were elicited (from 12 +/- 8.3 to 38 +/- 4.6 cmH(2)O,n = 10, p < 0.0001) with only a small rise of mBP (from 102 +/- 6.2 to 111 +/- 9.8 mmHg, n = 10, p < 0.005). Glutamate injections at dorsal sites evoked a rise of BlP (from 11 +/- 2.2 to 30 +/- 3.0 cmH(2)O (n = 5; p < 0.0001) with small changes in BP, whilst at ventral sites (n = 4) glutamate microinjections evoked changes in BP but not of BlP. In conclusion stimulation at different sites within HDA can elicit separate changes in BP and BlP.
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PMID:Effect of stimulation of anterior hypothalamic area on urinary bladder function of the anesthetized rat. 1531 45

Local metabolic changes are suggested to be involved in muscle pain development in humans. Nineteen women with chronic work-related trapezius myalgia (TM) and 20 healthy female controls (CON) were studied during baseline rest, 20 min repetitive low-force exercise, and 120 min recovery. Interstitial serotonin (5-HT), glutamate, lactate, pyruvate, and blood flow were determined by microdialysis in the trapezius muscle. Baseline pressure pain threshold (PPT) was lower (143+/-18 (TM) vs. 269+/-17 (CON)kPa) (mean+/-SEM), pain intensity (visual analogue scale, VAS) higher (33+/-5 vs. 2+/-1mm), muscle 5-HT higher (22.9+/-6.7 vs. 3.8+/-1.3 nmol/l), and glutamate higher (47+/-3 vs. 36+/-4 micromol/l) in TM than in CON (all P<0.05), whereas muscle blood flow was similar in groups. Furthermore, muscle pyruvate was higher (180+/-15 vs. 135+/-12 micromol/l) and lactate higher (4.4+/-0.3 vs. 3.1+/-0.3 mmol/l) in TM than in CON (P<0.001). In response to exercise, VAS and glutamate increased in both TM and CON (all P<0.05). In TM only, lactate and pyruvate increased significantly (P<0.02), whereas blood flow increased to similar levels in both groups. During the initial 20 min recovery period, blood flow remained increased in TM (P<0.005) whereas it decreased to baseline levels in CON. In conclusion, patients with chronic work-related TM have increased levels of muscle 5-HT and glutamate that were correlated to pain intensity (r=0.55, P<0.001) and PPT (r=-0.47, P<0.001), respectively. In addition, TM was associated with increased anaerobic metabolism, whereas a normal rise in blood flow was seen with exercise. These findings indicate that peripheral nociceptive processes are active in work-related TM.
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PMID:Increase in muscle nociceptive substances and anaerobic metabolism in patients with trapezius myalgia: microdialysis in rest and during exercise. 1556 88

A pH-responsive volume-change function was successfully introduced into a supramolecular hydrogel that contained GalNAc-appended (GalNAc=N-acetylgalactosamine) glutamate ester 1 by the simple mixing of it with an appropriate amount of 2 a or 2 b amphiphilic carboxylic acid. In the 1:1 mixture (1:2), the hydrogel swelled under neutral pH conditions, but shrank to almost half of its original volume under acidic pH conditions. The structure and pH response of the mixed hydrogel were characterized by using X-ray diffraction (XRD), confocal laser scanning microscopy (CLSM), transmission or scanning electron microscopy (TEM, SEM), and Fourier transform IR (FTIR) spectroscopy. Well-developed fibers formed a stable hydrogel by self-assembly, and under acidic conditions the charge of the carboxylic acid terminal (from the carboxylate anion) was neutralized and then these fibers became densely packed. This macroscopic pH response was also applied to the pH-triggered release of bioactive substances. In this mixed supramolecular hydrogel, the hydrogelator 1 provides a stable hydrogel structure and the additive 2 acts as a commander that is sensitive to an environmental pH signal. The present supramolecular copolymerization strategy should be useful for the construction of novel, stimuli-responsive, soft materials.
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PMID:pH-Responsive shrinkage/swelling of a supramolecular hydrogel composed of two small amphiphilic molecules. 1561 29

In brain injury, concentrations of extracellular excitatory amino acids are increased and stimulate glutamate receptors in general and the N-methyl-D-aspartate (NMDA)-preferring subtype in particular. That stimulation causes substantial calcium influx, which appears to initiate a cascade of events leading to neuronal death. Blockage of NMDA receptors with specific antagonists or noncompetitive ion channel blockers provides protection against excitatory amino acid-induced neurotoxicity. We previously reported that the NMDA receptor antagonist dizocilpine maleate improved the neurological severity score (NSS) after head trauma in rats. The present study was designed to determine whether ketamine, a NMDA receptor antagonist like dizocilpine maleate, improves neurological outcome following head trauma in rats. Thirty-two male Sprague-Dawley rats (235-250 g) were divided into four groups. Groups A and B were surgically prepared only. Groups C and D were surgically prepared and then a nonpenetrating impact was delivered to the cranium over the left hemisphere. Groups A and C received no treatment. Groups B and D were treated with ketamine, 180 mg/kg i.p., 1 h after head trauma. The NSS was determined at 1, 2, 4, 10, 24, and 48 h following head trauma. After killing at 48 h, cortical slices were taken adjacent to the lesion on the traumatized hemisphere and from comparable sites on the nontraumatized hemisphere to measure the tissue specific gravity and water content. Brains were then placed in 4% formaldehyde and the volume of hemorrhagic necrosis measured 4 days later. Head trauma increased the NSS and, in the traumatized hemisphere, decreased the specific gravity, increased the water content, and caused cerebral infarction. With ketamine, the NSS at 24 and 48 h following head trauma was 7.4 +/- 2.6 and 6.7 +/- 2.6 (mean +/- SEM), respectively, significantly improved compared to the NSS in the untreated group of 12.6 +/- 2.6 and 11.3 +/- 2.6, respectively (p <0.02, Mann-Whitney U test). With ketamine, the volume of hemorrhagic necrosis was 88.0 +/- 23.1 mm, significantly less than that in the untreated group (147.4 +/- 22.4 mm; p <0.05, unpaired t test). The brain tissue specific gravity and water content at 48 h and the rectal temperature at 4 and 48 h after head trauma were not significantly different between treated and untreated groups. It is concluded that in this model of closed cranial impact, ketamine improves neurological outcome and decreases the volume of hemorrhagic necrosis without altering brain edema.
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PMID:Ketamine decreases cerebral infarct volume and improves neurological outcome following experimental head trauma in rats. 1581 71

Previously, magnetic resonance spectroscopy studies of alterations in cerebral metabolite concentration during functional activation have been focused on phosphocreatine using 31P MRS and lactate using 1H MRS with controversial results. Recently, significant improvements on the spectral resolution and sensitivity of in vivo spectroscopy have been made at ultrahigh magnetic field strength. Using highly resolved localized short-TE 1H MRS at 11.7 T, we report metabolic responses of rat somatosensory cortex to forepaw stimulation in alpha-chloralose-anesthetized rats. The phosphocreatine/creatine ratio was found to be significantly decreased by 15.1 +/- 4.6% (mean +/- SEM, P < 0.01). Lactate remained very low (approximately <0.3 micromol/g w/w) with no statistically significant changes observed during forepaw stimulation at a temporal resolution of 10.7 min. An increase in glutamine and a decrease in glutamate and myo-inositol were also detected in the stimulated state. Our results suggest that, under the experimental conditions used in this study, increased energy consumption due to focal activation causes a shift in the creatine kinase reaction towards the direction of adenosine triphosphate production. At the same time, metabolic matching prevails during increased energy consumption with no significant increase in the glycolytic product lactate in the focally activated primary somatosensory cortex of alpha-chloralose-anesthetized rats.
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PMID:Metabolic alterations in focally activated primary somatosensory cortex of alpha-chloralose-anesthetized rats measured by 1H MRS at 11.7 T. 1618 71

The nasal route is used both for local therapies and, more recently, for the systemic administration of drugs, as well as for the delivery of peptides and vaccines. In this study the nasal administration of Carbamazepine (CBZ) has been studied using microspheres constituted by chitosan hydrochloride (CH) or chitosan glutamate (CG). Blank microspheres were also prepared as a comparison. The microspheres were produced using a spray-drying technique and characterized in terms of morphology (scanning electron microscopy, SEM), drug content, particle size (laser diffraction method) and thermal behaviour (differential scanning calorimetry, DSC). In vitro drug release studies were performed in phosphate buffer (pH 7.0). In vivo tests were carried out in sheep using the microparticles containing chitosan glutamate, chosen on the basis of the results of in vitro studies. The results were compared to those obtained after the nasal administration of CBZ (raw material) alone. For the evaluation of in vivo data statistical analysis was carried out using the unpaired t-test. Spray-drying was a good technique of preparation of CBZ-loaded microspheres. The loading of the drug into the polymeric network always led to an increase in the dissolution rate compared to CBZ raw material. The microspheres obtained using chitosan glutamate had the best behaviour both in vitro and in vivo. They increased the drug concentration in the serum when compared to the nasal administration of the pure drug (Cmax 800 and 25 ng/ml for microspheres and pure drug, respectively). The results obtained indicate that the loading of CBZ in chitosan glutamate microspheres increases the amount of the drug absorbed through the nose.
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PMID:Nasal administration of carbamazepine using chitosan microspheres: in vitro/in vivo studies. 1625 56

Secondary carnitine deficiencies are associated with metabolic disorders or may be the consequence of the side effects of some drugs. The mechanisms may be either a facilitated urinary excretion or an inhibited biosynthesis. Based on our earlier findings with drugs and benzoic acid analogue metabolites, in the present study, we studied the possible inhibitory effect of some benzoic acid analogue drugs. In the pathway of carnitine biosynthesis, we tested the last step, the hydroxylation of gamma-butyrobetaine (Bu) to carnitine in the liver. (Liver is the only organ in rats where this step takes place.) Of the 5 tested compounds, the p-aminomethylbenzoic acid (PAMBA) was found to be inhibitory. In tracer experiments with radioactive Bu, PAMBA (a single injection of 1.2 mmol/kg) reduced the conversion of [Me-(3)H]Bu to [Me-(3)H]carnitine from 62.6% +/- 5.11% to 46.8% +/- 5.02% (means +/- SEM, P < .02). This single dose also markedly reduced the conversion of loading amount of exogenous unlabeled Bu, as measured by enzymatic analysis of carnitine. The conversion of endogenous Bu was also hampered by long-term administration of PAMBA, as indicated by increased Bu and decreased carnitine levels. Furthermore, single injection of PAMBA markedly reduced the Glu level in the liver from 2.87 +/- 0.17 to 1.42 +/- 0.11 mumol/g (P < .001). Trying to get closer to a mechanism by which the flux through the Bu hydroxylase was depressed, we supposed that alfa-ketoglutarate (alpha-KG), an obligatory cofactor of the enzyme, was also be depressed. It was expected because alpha-KG is a reversible copartner of l-glutamate through the Glu-dehydrogenase reaction. We found that PAMBA reduced the alpha-KG level from 207 +/- 17.5 to 180 +/- 19.1 nmol/g (means +/- SEM, P < .02). Considering the conditions of the enzyme in vitro and in vivo, this decrease may contribute to the decreased in vivo flux through the butyrobetaine hydroxylase enzyme.
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PMID:Effect of aromatic ring-containing drugs on carnitine biosynthesis in rats with special regard to p-aminomethylbenzoic acid. 1631 Oct 89

It has recently been shown that the antianginal drug bepridil (BEP) activates mitochondrial ATP-sensitive potassium (mitoK(ATP)) channels and thus confers cardioprotection. Our aim was to investigate whether BEP could induce preconditioning in cultured rat cortical neurons. Although BEP depolarized isolated and in situ mitochondria and increased reactive oxygen species generation, no acute protection was observed. However, a 3-day BEP-treatment elicited dose-dependent delayed neuroprotection against 180 min of oxygen-glucose deprivation (cell viability: untreated, 52.5 +/- 0.85%; BEP 1 micromol/L, 59.6 +/- 1.53%*; BEP 2.5 micromol/L, 71.9 +/- 1.23%*; BEP 5 micromol/L, 95.3 +/- 0.89%*; mean +/- SEM; *p < 0.05 vs. untreated) and 60 min of glutamate excitotoxicity (200 micromol/L; cell viability: untreated, 54.1 +/- 0.69%; BEP 1 micromol/L, 61.2 +/- 1.19%*; BEP 2.5 micromol/L, 78.1 +/- 1.67%*; BEP 5 micromol/L, 91.2 +/- 1.20%*; mean +/- SEM; *p < 0.05 vs. untreated), and inhibited the reactive oxygen species surge upon glutamate exposure. The protection was antagonized with co-application of the superoxide dismutase mimetic M40401, but not with reduced glutathione, catalase, or with the mitoK(ATP) blocker 5-hydroxydecanoate. Furthermore, BEP treatment resulted in increased levels of phosphorylated protein kinase C, manganese-dependent superoxide dismutase, glutathione peroxidase, and Bcl-2. Our results indicate that BEP induces delayed neuronal preconditioning which is dependent on superoxide generation but perhaps not on direct mitoK(ATP) activation.
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PMID:Neuronal preconditioning with the antianginal drug, bepridil. 1739 52

Hippocampal output is increased in affective disorders and is mediated by increased glutamatergic input via N-methyl-D-aspartate (NMDA) receptor and moderated by antidepressant treatment. Activation of NMDA receptors by glutamate evokes the release of nitric oxide (NO) by the activation of neuronal nitric oxide synthase (nNOS). The human hippocampus contains a high density of NMDA receptors and nNOS-expressing neurons suggesting the existence of an NMDA-NO transduction pathway which can be involved in the pathogenesis of affective disorders. We tested the hypothesis that nNOS expression is increased in the human hippocampus from affectively ill patients. Immunocytochemistry was used to demonstrate nNOS-expressing neurons in sections obtained from the Stanley Consortium postmortem brain collection from patients with major depression (MD, N = 15), bipolar disorder (BD, N = 15), and schizophrenia (N = 15) and from controls (N = 15). nNOS-immunoreactive (nNOS-IR) and Nissl-stained neurons were counted in entorhinal cortex, hippocampal CA1, CA2, CA3, and CA4 subfields, and subiculum. The numbers of Nissl-stained neurons were very similar in different diagnostic groups and correlated significantly with the number of nNOS-IR neurons. Both the MD and the BD groups had greater number of nNOS-IR neurons/400 microm(2) in CA1 (mean +/- SEM: MD = 9.2 +/- 0.6 and BD = 8.4 +/- 0.6) and subiculum (BD = 6.7 +/- 0.4) when compared to control group (6.6 +/- 0.5) and this was significantly more marked in samples from the right hemisphere. These changes were specific to affective disorders since no changes were seen in the schizophrenic group (6.7 +/- 0.8). The results support the current view of the NMDA-NO pathway as a target for the pathophysiology of affective disorders and antidepressant drug development.
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PMID:Expression of neuronal nitric oxide synthase in the hippocampal formation in affective disorders. 1839 56


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