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At least 721 records · Page 40Linked to original sources
PubMed1988

Sustained intermittent release of gonadotropin-releasing hormone in the prepubertal male rhesus monkey induced by N-methyl-DL-aspartic acid.

The purpose of the present study was to determine whether gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus of the prepubertal monkey may be prematurely provoked into producing a sustained train of intermittent GnRH release N-methyl-DL-aspartic acid (NMA), an analog of the putative excitatory neurotransmitter aspartate, was used to stimulate the hypothalamus. In order to utilize pituitary luteinizing hormone (LH) secretion as a bioassay of hypothalamic GnRH release, juvenile males were castrated and the responsiveness of their gonadotrophs to GnRH was enhanced prior to the study with a chronic intermittent intravenous infusion of the synthetic decapeptide (0.1 microgram/min for 3 min every hour). Treatment with this regimen of GnRH, which appears to provide the pituitary gonadotrophs with a hypophysiotropic stimulus similar to that produced by the hypothalamus of castrated adults, elicited a pattern of pulsatile LH secretion in prepubertal animals similar to that observed in the open-loop situation in adults. This episodic pattern of LH release was sustained without decrement following termination of GnRH priming and initiation of an intermittent intravenous infusion of NMA (4.5-6.5 mg NMA/kg body weight/pulse, administered over 1 min) delivered at a frequency of 1 pulse/1 h for 50 h. In contrast, an intermittent infusion of the vehicle employed to administer NMA (saline) failed to maintain LH secretion. Administration of the same dose of NMA at a slower frequency of 1 pulse/2 h for 52 h, while also sustaining LH secretion without decrement, resulted in an exaggeration in the LH response.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Studies on age estimation using racemization of aspartic acid in cementum.

An attempt was made to estimate the age of cementum using the racemization method, which focuses on the ratio of D- and L-aspartic acids (referred to as the 'D/L ratio'). Using the whole cementum, the correlation coefficients between the D/L ratio and age were r = 0.984 to 0.997. When the use of incisors and premolars was compared, the former gave better results than the latter. We then made a comparison of cementum, enamel and dentin, using a first premolar from the same individual. For each component tissue the correlation of D/L ratio with the actual age was calculated and the highest value was shown for dentin at r = 0.992, followed by cementum at r = 0.988 and enamel at r = 0.961. These results show that the racemization reaction in cementum proceeds at a constant rate, and confirm that cementum, like dentin, is a tissue with very low metabolism. Therefore, it is clear that accurate estimation of age is practically possible using the amino acid racemization method for cementum.

Adult↗
PubMedDate not supplied

[Stability of the biocatalysts of L-aspartic acid synthesis based on immobilized Escherichia coli cells].

Experiments were carried out to investigate the process of a continuous enzymatic synthesis of L-aspartic acid from ammonium fumarate in uniform filling flow reactors. Escherichia coli (Soviet strain 85) cells immobilized in polyacrylamide gel granules reinforced by a solid carrier were used as biocatalysts. The conditions, under which a high aspartase activity of the biocatalyst and a stable hydrodynamic performance of the reactor were maintained, were determined. The main kinetic characteristics of a continuous performance of the reactor for 150 days were obtained.

Acrylic Resins↗
PubMed1991

Further characterization of carboxymethylated aspartic acid agarose. Purification of human alpha 2-macroglobulin and hemopexin.

alpha 2-Macroglobulin and hemopexin were purified by affinity chromatography on a recently introduced chelating matrix, i.e., carboxymethylated aspartic acid agarose, coupled with cobalt(II). Adsorption was performed at neutral pH and the proteins were eluted by lowering the pH to 5.0. An alternative method for desorption as well as comparison with iminodiacetic acid agarose coupled with cobalt(II) is also described.

Animals↗
PubMed1987

Evidence that neurons of the paraventricular nucleus of the hypothalamus with projections to the spinal cord are sensitive to the toxic effects of N-methyl aspartic acid.

Controversy exists concerning the sensitivity of neurons of the paraventricular nucleus (PVN) of the hypothalamus to the toxic effects of N-methyl aspartic acid (NMA). To further investigate this problem, male golden hamsters (Mesocricetus auratus) received unilateral intrahypothalamic injections of NMA, coupled with injections of horseradish peroxidase into the area of the spinal cord which receives projections from the PVN. Histological evaluation of the brains showed that the NMA injections destroyed PVN neurons that project to the spinal cord. These results are discussed in reference to previous reports on the effects of NMA injections on photoperiod-dependent seasonal cycles in hamsters.

Animals↗
PubMed1996

Phase II trial of low-dose N-(phosphonacetyl)-disodium L-aspartic acid and high-dose 24-hour infusional 5-fluorouracil in advanced gastric adenocarcinoma. A Southwest Oncology Group study.

N-(phosphonacetyl)-disodium L-aspartic acid (PALA) demonstrates a synergistic antitumor effect when combined with 5-Fluorouracil (5-FU) in in vitro studies. In a Phase II trial, 23 eligible patients with unresectable or metastatic adenocarcinoma of the stomach were treated with weekly i.v. bolus PALA (250 mg/M2) followed 24 hours later by a 24-hour infusion of 5-FU (2600 mg/M2) for an initial period of 8 weeks. No objective responses were noted. PALA and 5-FU is inactive against gastric adenocarcinoma at the doses and schedule used in this trial.

Adenocarcinoma↗
PubMed1990

Glycine-231 residue of the mouse mitochondrial protonmotive cytochrome b: mutation to aspartic acid deranges electron transport.

The mouse LA9 HQN-R11 cytochrome b mutant, in which the glycine residue at position 231 is replaced by aspartic acid, has increased resistance to all inhibitors of the Qn redox center. It is shown here that this single amino acid alteration has multiple and unexpectedly diverse effects upon the mitochondrial protonmotive bc1 complex. (1) The specific activities of both succinate- and ubiquinol-cytochrome c oxidoreductases in isolated mitochondria are reduced by approximately 65% in the mutant. The parallel reductions in both oxidoreductase activities are not compatible with simple Q pool kinetics for mitochondrial electron transport. (2) There is also a reduction in the relative concentration of cytochrome b in the mutant when calculated on the basis of mitochondrial protein; this decrease does not account for more than a small portion of the reduced catalytic fluxes. (3) The increased antimycin resistance of the mutant is lost upon solubilization by the detergent dodecyl maltoside of the bc1 complex from mitochondria. (4) In pre-steady-state assays of cytochrome b reduction by quinol, the mutant shows a reduced extent of reduction. It was observed in other experiments that there was less oxidant-induced extrareduction of cytochrome b in the mutant. These results could arise from a lowering of the midpoint potentials of both the cytochrome b-562 and cytochrome b-566 heme groups. Alternatively, these effects may reflect changes at the Qp and Qn quinone/quinol binding sites. (5) An unexplained observation for the mutant is the increased rate of cytochrome c1 reduction in the presence of myxothiazol. (6) These functional alterations in the LA9 HQN-R11 mutant are not accompanied by detectable changes in the spectral properties of the cytochrome b or c1 heme groups.

Antimycin A↗
PubMed2006

Role of activator protein-1 on the effect of arginine-glycine-aspartic acid containing peptides on transforming growth factor-beta1 promoter activity.

While arginine-glycine-aspartic acid-based peptidomimetics have been employed for the treatment of cardiovascular disorders and cancer, their use in other contexts remains to be explored. Arginine-glycine-aspartic acid-serine induces Transforming growth factor-beta1 transcription in human mesangial cells, but the molecular mechanisms involved have not been studied extensively. We explored whether this effect could be due to Activator protein-1 activation and studied the potential pathways involved. Addition of arginine-glycine-aspartic acid-serine promoted Activator protein-1 binding to its cognate sequence within the Transforming growth factor-beta1 promoter as well as c-jun and c-fos protein abundance. Moreover, this effect was suppressed by curcumin, a c-Jun N terminal kinase inhibitor, and was absent when the Activator protein-1 cis-regulatory element was deleted. Activator protein-1 binding was dependent on the activity of integrin linked kinase, as transfection with a dominant negative mutant suppressed both Activator protein-1 binding and c-jun and c-fos protein increment. Integrin linked kinase was, in turn, dependent on Phosphoinositol-3 kinase activity. Arginine-glycine-aspartic acid-serine stimulated Phosphoinositol-3 kinase activity, and Transforming growth factor-beta1 promoter activation was abrogated by the use of Phosphoinositol-3 kinase specific inhibitors. In summary, we propose that arginine-glycine-aspartic acid-serine activates Integrin linked kinase via the Phosphoinositol-3 kinase pathway and this leads to activation of c-jun and c-fos and increased Activator protein-1 binding and Transforming growth factor-beta1 promoter activity. These data may contribute to understand the molecular mechanisms involved in the cellular actions of arginine-glycine-aspartic acid-related peptides and enhance their relevance as these products evolve into clinical therapeutic use.

Cardiovascular Diseases↗
PubMed1983

The effects of oral administration of salts of aspartic acid on the metabolic response to prolonged exhausting exercise in man.

The effects of the oral administration of salts of aspartic acid on endurance capacity and metabolic responses to prolonged bicycle exercise have been investigated. Previous reports in man and in animals have suggested that this treatment can increase the capacity to perform muscular work by virtue of its effect on circulating ammonia levels. Eight healthy young male subjects exercised to exhaustion on a bicycle ergometer at a work load requiring approximately 75% of maximum oxygen uptake. This work test was performed after placebo administration or after ingestion of 6 g of potassium-magnesium aspartate over a 24-h period, using a double-blind protocol. Exhaustion was reached after 82.7 +/- 23.5 min (mean +/- SD) following aspartate treatment and after 85.4 +/- 26.5 min following the placebo. No differences in the blood glucose, lactate, or ammonia concentrations or in the plasma free fatty acid concentration between the two treatments were observed. The respiratory exchange ratio was the same on both occasions. These results show no beneficial effect of oral aspartate administration on work capacity in man and also suggest that the metabolic processes that occur during exercise are not influenced by this treatment.

Adult↗
PubMed2004

Age estimation from aspartic acid racemization of root dentin by internal standard method.

In this study, we investigated the application of the internal standard method to determine age from aspartic acid (Asp) racemization. D-Methionine (D-Met) and D-norleucine (D-Nleu) were tested as internal standards for the purpose of validating the derivatization and gas chromatographic measurements. Using a set of standard amino acids plus the internal standards in constant volume, calibration plots with reasonable linearity (R > 0.98) were constructed. Based on the analysis of sample chromatograms, D-Met appeared to meet the criteria for internal standards, hence it was selected for use in D- and L-Asp quantification. The correlation between dentin age and D-/L-Asp ratios from the peak areas as well as from the absolute concentrations was investigated. Correlation coefficients were calculated as 0.98 and 0.90, respectively. The slight decrease in accuracy was attributed to the conversion of D-Asp/D-Met ratios to concentrations employing the calibration curves figured from pure Asp. Because the application of the internal standard method produced reproducible and precise measurements, the employment of internal standards in age estimation based on Asp racemization appears to provide quality assurance by avoiding possible errors arising from sample preparation.

Adolescent↗
PubMed2000

In vitro cytotoxic effect of N-(phosphonacetyl)-L-aspartic acid in liposome against C-26 murine colon carcinoma.

We have investigated the in vitro cytotoxic effect of liposome-encapsulated N-(phosphonacetyl)-L-aspartic acid (PALA) against C-26 murine colon cancer cells, and have compared it in this regard to free PALA. Three different PALA-containing liposomal formulations using distearoylphosphatidylcholine (DSPC), distearoylphosphatidylglycerol (DSPG), and polyethyleneglycol-derivatized distearoylphosphatidylethanolamine (PEG-DSPE) were made and their cytotoxicity was measured. In 72 hr continuous exposure experiment with C-26 cells, the 50% growth inhibitory concentration (IC50) of DSPG-PALA liposome formulation was 0.09 microM, which showed about 65-fold more potent than unencapsulated free PALA (5.1 microM). Similar degree of increase in cytotoxicity was also observed in 1 hr exposure experiment. However, the IC50 of PEG-DSPE-PALA liposome and DSPC-PALA liposome were 10.7 microM and 11.8 microM, respectively, which showed slightly less potent than unencapsulated free PALA. Physical characteristics of PALA-liposomes, such as the size and drug:lipid ratio were also determined. In conclusion, negatively-charged DSPG-PALA liposome showed the highest cytotoxic effect among tested on the C-26 cells in vitro.

Animals↗
PubMed2006

D-aspartic acid in the nervous system of Aplysia limacina: possible role in neurotransmission.

In the marine mollusk Aplysia limacina, a substantial amount of endogenous D-aspartic acid (D-Asp) was found following its synthesis from L-aspartate by an aspartate racemase. Concentrations of D-Asp between 3.9 and 4.6 micromol/g tissue were found in the cerebral, abdominal, buccal, pleural, and pedal ganglia. In non nervous tissues, D-Asp occurred at a very low concentration compared to the nervous system. Immunohistochemical studies conducted on cultured Aplysia neurons using an anti-D-aspartate antibody demonstrated that D-Asp occurs in the soma, dendrites, and in synaptic varicosities. Synaptosomes and synaptic vesicles from cerebral ganglia were prepared and characterized by electron microscopy. HPLC analysis revealed high concentrations of D-Asp together with L-aspartate and L-glutamate in isolated synaptosomes In addition, D-Asp was released from synaptosomes by K+ depolarization or by ionomycin. D-Asp was one of the principal amino acids present in synaptic vesicles representing about the 25% of total amino acids present in these cellular organelles. Injection of D-Asp into live animals or addition to the incubation media of cultured neurons, caused an increase in cAMP content. Taken as a whole, these findings suggest a possible role of D-Asp in neurotransmission in the nervous system of Aplysia limacina.

Animals↗
PubMed1995

Complex involvement of nitric oxide and cGMP at N-methyl-D-aspartic acid receptors regulating gamma-[3H]aminobutyric acid release from striatal slices.

Whilst the depolarization of postsynaptic N-methyl-D-aspartic acid (NMDA) receptors leads to an influx of Ca2+ and subsequent synthesis of nitric oxide (NO), we examined roles for NO at striatal NMDA receptors regulating transmitter release. In superfused rat striatal slices, NMDA-evoked release of gamma-[3H]aminobutyric acid ([3H]GABA) was investigated in the presence of nitrergic drugs. NMDA-induced release of [3H]GABA was attenuated by D-2-aminophosphonopentanoate, tetrodotoxin and omission of Ca2+. L-Arginine enhanced NMDA-evoked release of [3H]GABA, but exogenous NO donors were ineffective. Inhibitors of NO synthase (NG-nitro- and NG-amino-L-arginine) and guanylate cyclase (LY83583) elevated release. Since NMDA-evoked release of [3H]GABA was partially tetrodotoxin-sensitive, nitrergic-linked NMDA receptors regulating the release are both pre- and extrasynaptic. Thus not only does NO arise from multiple sites, and involve NMDA receptors with their redox site insensitive to exogenous NO donors, but the NMDA receptors are under the influence of nitrergic and cGMP-linked negative feedback mechanisms.

Aminobutyrates↗
PubMedDate not supplied

The treatment with L-aspartic acid of persons addicted to opiates.

Two clients addicted to codeine, two to heroin and four to opium tincture were orally administered 2 g L-aspartic acid four times daily for up to five days on an out-patient basis. The clients were withdrawn from the drugs on which they were physically dependent by gradually decreasing the amount of the drug abused. Some mild abstinence signs and symptoms were observed during the treatment, while the clients showed a marked improvement in social contacts and behaviour. At the end of the treatment period, and during the subsequent two weeks, not one of the treated persons showed any sign of the abstinence syndrome or expressed a feeling of need for the compulsive intake of the drug which had been abused.

Adult↗
PubMed1994

Brain N-acetyl-L-aspartic acid in Alzheimer's disease: a proton magnetic resonance spectroscopy study.

This study was performed in order to measure changes in brain N-acetyl-L-aspartic acid (NAA) in post-mortem brain tissue in Alzheimer's disease (AD) in comparison to normal control subjects using the technique of magnetic resonance spectroscopy. Brain tissue was obtained at autopsy and frozen until use, from seven patients diagnosed according to current research criteria for AD and 7 control subjects. Detailed clinical evaluations were available for all the dementia cases. Representative brain samples were obtained from three neocortical regions and a limbic region (parahippocampal gyrus) in white and grey matter. NAA was quantified on perchloric acid extracts using proton nuclear magnetic resonance (NMR) spectroscopy. Regional NAA did not vary significantly with age. In AD, reductions were present in the grey matter of the neocortex but not in the white matter. Within the parahippocampal gyrus there were reductions in both tissue types; only cortical levels correlated with clinical scales of dementia severity. A pattern of increasing correlation was observed between dementia severity as measured by the mini mental state examination during life and NAA levels from brain areas of increasing pathological predilection in AD. These post-mortem studies show reductions in brain NAA in AD which correlate with dementia severity during life and which support the use of future in vivo NAA spectroscopic images in the evaluation of AD patients.

Aged↗
PubMed2006

Replication of the association of the aspartic acid repeat polymorphism in the asporin gene with knee-osteoarthritis susceptibility in Han Chinese.

A genetic association of osteoarthritis (OA) and functional polymorphisms in the aspartic acid (D) repeat of the asporin gene was reported in Japanese and European Caucasians; however, the results were controversial. Our objective was to evaluate whether the D repeat polymorphism was associated with knee OA in Han Chinese. The D repeat polymorphism was genotyped in 218 patients who suffered from primary symptomatic knee OA with radiographic confirmation and in 454 age-matched controls, and the allelic association of the repeat was examined. Frequencies of the D13 and D14 alleles were similar to those of Japanese, but different from those of European Caucasians. The D14 allele was significantly over-represented in knee OA patients (P=0.0013; odds ratio 2.04; 95% confidence interval 1.32-3.15). D14 was more frequent in early-onset patients than in late-onset patients (P=0.043) and the age at onset in patients with D14 was earlier (P=0.028; log-rank test). Thus, the association of the D14 allele with knee OA susceptibility was replicated in Han Chinese. This was the first instance that association of the OA susceptibility gene was definitely replicated between different ethnic groups.

Adult↗
PubMed1993

N-methyl-D,L-aspartic acid differentially affects LH release and LHRH mRNA levels in estrogen-treated ovariectomized control and androgen-sterilized rats.

Excitatory amino acids such as N-methyl-D,L-aspartic acid (NMDA) are thought to play an important role in the regulation of gonadotropin secretion. NMDA induces significant increases in plasma LH in a variety of animal models and these effects occur by activation of neural processes involved in excitation of LHRH neurons rather than by a direct action on the pituitary gland. We have taken advantage of this information to study the effects of NMDA on LH release and on changes in levels of LHRH mRNA in single neurons of adult rats treated neonatally with a high dosage of androgen. While iv NMDA evoked an increase in plasma LH in estrogen-treated ovariectomized control and androgen-sterilized rats (ASR), significantly less LH was released in ASR. LHRH mRNA levels in the organum vasculosum of the lamina terminalis (OVLT), the rostral (r), media (m) and caudal (c) preoptic (POA) regions were quantitated using in situ hybridization histochemistry and quantitative image analysis methods. LHRH mRNA levels in untreated controls and ASR did not differ in any of the brain regions examined. Within 1 h after NMDA, LHRH mRNA had increased significantly in OVLT and rPOA but not in mPOA and cPOA neurons of control rats and these mRNA levels remained elevated for 4 h. In contrast, NMDA treatment of ASR did not affect basal levels of LHRH mRNA in any region of the rostral hypothalamus. These observations suggest that neonatal androgen treatment of female rats either directly or indirectly affects the responsiveness of LHRH neurons to NMDA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗