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  • 1
    Electronic Resource
    Electronic Resource
    Determination of Kainic Acid-Induced Release of Nitric Oxide Using a Novel Hemoglobin Trapping Technique with Microdialysis (1993)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 61 (1993), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We have demonstrated the usefulness of a novel hemoglobin-trapping technique to quantify nitric oxide (NO) concentrations in vivo. Concentric microdialysis probes were implanted into the hippocampus of rats under urethane anesthesia and perfused with 1 μM oxyhemoglobin in artificial CSF to sequester NO in extracellular fluid. The concentration of methemoglobin was then determined spectrophotometrically. The basal level of NO in hippocampus was 2.2 ± 0.5 nM(in vitro sensitivity of the probe was 0.2 nM). Administration of 13 mg/kg, i.p., of kainic acid (KA) produced a maximal 5.3-fold increase at 100 min in NO levels (11.8 ± 0.2 nM). This response was significantly attenuated by pretreatment with the NO synthase inhibitor N-monomethyl-L-arginine (50 mg/kg, 30 min before KA). These results demonstrate that a microdialysis probe using a novel hemoglobin-trapping technique possesses adequate sensitivity to determine the basal levels of NO and document the ability of KA to increase these levels via a NO synthase-mediated mechanism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1993.tb07475.x
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  • 2
    Electronic Resource
    Electronic Resource
    Changes in Brain Levels of Acidic, Basic, and Neutral Amino Acids After Consumption of Single Meals Containing Various Proportions of Protein (1983)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 41 (1983), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Rats fasted overnight were allowed to consume single meals containing 0, 18, or 40% protein or continued to fast; after 2 h, brains and sera were taken and assayed for various amino acids. In general, serum levels of most amino acids were reduced by the 0% protein meal and elevated by the high-protein meal when compared with those associated with fasting conditions. Exceptions were those not diminished by the 0% protein meal (tryptophan, methionine, proline) and those increased (alanine) or decreased (glycine) by all of the test meals. Amino acids exhibiting the broadest normal ranges (estimated by comparing their serum levels after 40% protein with those after 0% protein) were tyrosine, leucine, valine, isoleucine, and proline; serum lysine and histidine, two basic amino acids, also varied more than threefold. Brain levels of lysine, histidine, and some of the large neutral amino acids (LNAAs) also exhibited clear relationships to the protein content of the test meal: those of valine, leucine, and isoleucine were depressed by the 0% protein but increased (compared with 0% protein) when protein was added to the meal: brain tyrosine was increased by all of the test meals in proportion to their protein contents; tryptophan, phenylalanine, and glutamate were increased after the 0% protein meal but not by protein-containing meals; brain lysine, histidine, and methionine were increased after the high-protein meal, and brain alanine was increased slightly by all of the meals. For each of the LNAAs, significant correlations were observed between its brain level in any animal and the ratio of its serum concentration to the sum of the concentrations of its LNAA competitors (for blood-brain barrier transport). For valine, tyrosine, lysine, and histidine, significant correlations were obtained between their brain and serum levels.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1983.tb09045.x
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  • 3
    Electronic Resource
    Electronic Resource
    Branched chain amino acids decrease tardive dyskinesia symptoms (1999)
    Springer
    Psychopharmacology 143 (1999), S. 358-364 
    Details
    ISSN: 1432-2072
    Keywords: Key words Brain availability ; Branched chain amino acid ; Carrier-mediated transport ; Large neutral amino acid ; Medical food ; Phenylalanine ; Phenylketonuria ; Protein ; Tardive dyskinesia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: Prior studies had suggested (a) that a lessened ability to clear ingested forms of the large neutral amino acid (LNAA), phenylalanine (Phe), was associated with having tardive dyskinesia (TD), and (b) that greater availability of a group of LNAA, the branched chain amino acids (BCAA), concomitant with the lower availability of Phe to the brain are associated with a decrease in TD symptoms. The present study was then conducted to test whether increasing the daily intake of the BCAA would decrease the symptoms of TD. Methods: A 2-week trial of a BCAA medical food administered three times a day was conducted in nine men with long neuroleptic treatment histories. Frequency counts of TD movements were collected by videotape throughout the trial and these tapes were analyzed in blind random sequence for both patient and time for TD symptom level changes subsequent to completion of the trial. Plasma levels of the LNAA were also collected throughout the trial. Results: A statistically significant decrease in the level of TD symptoms was observed for the sample. The symptom changes were also clinically significant in that six of the nine subjects had symptom decreases of at least 58%, with all subjects having a decrease of at least 38%. BCAA administration increased plasma BCAA concentrations and BCAA/LNAA ratios and decreased plasma Phe concentrations and the Phe/LNAA ratio. Analyses indicated a strong significant correlation between the percent increase in the plasma BCAA values at the first administration and the percent improvement in TD over the trial in eight of the nine subjects. Conclusions: The BCAA show promise as a treatment for TD. The decrease in TD symptoms seen in the trial may have been modulated by the BCAA treatment-induced increased availability of the BCAA and decreased availability of Phe to the brain.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050959
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  • 4
    Electronic Resource
    Electronic Resource
    Phenylalanine kinetics are associated with tardive dyskinesia in men but not in women (1999)
    Springer
    Psychopharmacology 143 (1999), S. 347-357 
    Details
    ISSN: 1432-2072
    Keywords: Key words Amine neurotransmitter supersensitivity ; Blood-brain barrier transport ; Gastric emptying ; Hepatic clearance ; Kinetics ; Large neutral amino acid ; Movement disorder ; Neuroleptic ; Neurotransmitter precursors ; Neurotransmitter synthesis ; Phenylalanine ; Plasma absorption ; Sex difference ; Tardive dyskinesia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: An association between tardive dyskinesia (TD) and severely impaired metabolism of the large neutral amino acid (LNAA), phenylalanine (Phe) was defined in a group of mentally retarded patients. Subsequently, an altered kinetics of Phe was associated with TD in men with schizophrenia based on plasma analyses subsequent to the ingestion of a protein meal. Methods: In the present study, a standardized oral challenge of pure Phe (100 mg/kg in 170 ml orange juice) was administered to psychiatric patients of both sexes (n = 312), with and without TD after an overnight fast. Plasma LNAA levels were assayed both fasting and 2 h subsequent to the ingestion of the challenge. The extent of the increase in plasma Phe levels 2 h following a standardized challenge is determined by the sum of the kinetic processes of plasma absorption, tissue distribution, metabolism and elimination. Results: The study hypothesis, that TD would be associated with significantly higher post-challenge plasma Phe indices of an absolute plasma Phe level and plasma Phe/LNAA ratio (a brain availability measure), was verified for the study men (n = 209), but not for the study women (n = 103). Conclusions: The demonstrated altered kinetics of Phe in men with TD indicates a greater availability of Phe to the brain in these men. We suggest that the disorder may be related to the effects of this greater availability. Such effects could be the direct neurotoxic effects of Phe and its metabolites and/or the modulating effects of these compounds on the synthesis of the monoamine neurotransmitters. The fact that TD (Yes/No) group differences in post-challenge plasma Phe indices were not seen for the study women suggests the possibility of a sex difference in the biology of TD that we propose may be reflective of the young age of the study sample.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050958
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  • 5
    Electronic Resource
    Electronic Resource
    Extracellular glutamate increases in rostral ventrolateral medulla during static muscle contraction (1998)
    Springer
    Pflügers Archiv 435 (1998), S. 465-471 
    Details
    ISSN: 1432-2013
    Keywords: Key words Arterial pressure ; Microdialysis ; Excitatory amino acid ; Exercise ; Pressor Reflex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The ventrolateral medulla is an important site involved in increases in arterial pressure and heart rate during static muscle contraction. Glutamate, an excitatory amino acid neurotransmitter, appears to play a role in mediating these responses. We measured glutamate concentration in the extracellular fluid of the rostral ventrolateral medulla during static muscle contraction in anesthetized rats. A 2-min tibial nerve stimulation-evoked muscle contraction increased blood pressure by 30 ± 4 mmHg and heart rate by 32 ± 4 bpm. Extracellular glutamate in the rostral ventrolateral medulla also increased from 9 ± 1 pmol/4 μl to 14 ± 1 pmol/4 μl. Results were repeatable over two subsequent contractions. Tibial nerve stimulation following neuromuscular blockade did not elicit changes in blood pressure, heart rate or extracellular fluid glutamate. Data demonstrate that muscle contraction increases extracellular fluid concentration of glutamate in the rostral ventrolateral medulla, suggesting that rostral ventrolateral medullary glutamate release is a neurochemical change associated with cardiovascular responses during static muscle contraction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050540
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  • 6
    Electronic Resource
    Electronic Resource
    Use of a Hemoglobin-Trapping Approach in the Determination of Nitric Oxide in In Vitro and In Vivo Systems (1998)
    Springer
    Neurochemical research 23 (1998), S. 815-820 
    Details
    ISSN: 1573-6903
    Keywords: Nitric oxide ; microdialysis ; hemoglobin-trapping technique
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We describe methods for measuring the release of nitric oxide (NO) derived from organic nitrates in vitro, using triple wavelength and difference spectrophotometry in the presence and absence of concentric microdialysis probes. These methods are based on the ability of NO to oxidize oxyhemoglobin (OxyHb) to methemoglobin (MetHb) quantitatively in aqueous solution. Isosorbide dinitrate (ISDN), a thiol-dependent organic nitrate, increased MetHb concentration in 45 min from 2.47 ± 0.47 to 4.15 ± 0.12 μM (p 〈 0.05) and decreased OxyHb concentration from 2.13 ± 0.35 to 0.33 ± 0.26 μM (p 〈 0.05) at 37°C. At 27°C, the OxyHb concentration was not significantly altered (2.04 ± 0.23 to 1.60 ± 0.04 μM) by ISDN, nor was the MetHb concentration (from 2.68 ± 0.50 to 2.59 ± 0.25 μM). Sodium nitroprusside (SNP), a thiol-independent organic nitrate, increased MetHb concentrations in 30 min from 4.21 ± 0.26 to 6.00 ± 0.56 μM (p 〈 0.05) at 37°C, and from 4.23 ± 0.39 to 5.90 ± 0.43 μM (p 〈 0.01) at 27°C. SNP also decreased OxyHb concentrations in 30 min from 1.99 ± 0.32 to 0.13 ± 0.12 μM (p 〈 0.01) at 37°C, and from 2.25 ± 0.31 to 0.13 ± 0.09 μM (p 〈 0.01) at 27°C. Difference spectrophometry indicated that 0.25-5 mM SNP significantly increased NO production in a dose-dependent fashion. This hemoglobin-trapping technique was also useful in quantifying the concentrations of NO released from SNP in aqueous solution in vitro, using concentric microdialysis probes. The NO concentration following exposure to SNP was 530 ± 50 nM, as determined using the difference spectrophotometric technique. To demonstrate the applicability of this technique to in vivo microdialysis, we implanted concentric microdialysis probes into hippocampus and cerebellum of conscious and anesthetized rats. Baseline NO concentrations in hippocampus of conscious and anesthetized rats were 11 ± 2 nM and 23 ± 9 nM, respectively, while in the cerebellum NO concentrations were 28 ± 9 nM and 41 ± 20 nM, respectively. These results demonstrate that microdialysis using a novel hemoglobin-trapping technique possesses adequate sensitivity to measure the NO levels produced from organic nitrates in aqueous solutions, and further document the applicability of this approach to in vivo systems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1022475830200
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